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1. CA2353574 - ANALOGUES OF GLP-1

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ANALOGUES OF GLP-1
Background of the Invention
The present invention is directed to peptide analogues of glucagon-like peptide-1, the pharmaceutically-acceptable salts thereof, to methods of using such analogues to treat mammals and to pharmaceutical compositions useful therefor comprising said analogues.
Glucagon-like peptide-1 (7-36) amide (GLP-1) is synthesized in the intestinal L-cells by tissue-specific post-translational processing of the glucagon precursor preproglucagon (Varndell, J.M., et al., J. Histochem Cytochem, 1985:33:1080-6) and is released into the circulation in response to a meal.
The plasma concentration of GLP-1 rises from a fasting level of approximately 15 pmol/L to a peak postprandial level of 40 pmol/L. It has been demonstrated that, for a given rise in plasma glucose concentration, the increase in plasma insulin
approximately threefold greater when glucose is administered orally compared with intravenously (Kreymann, B., et al., Lancet 1987:2, 1300-4). This alimentary enhancement of insulin release, known as the incretin effect, is primarily humoral and GLP-1 is now thought to be the most potent physiological incretin in humans.
In addition to the insulinotropic effect, GLP-1 suppresses glucagon secretion, delays gastric emptying (Wettergren A., et al., Dig Dis Sci 1993:38:665-73) and may enhance peripheral glucose disposal (D'Alessio, D.A. et at., J. Clin
Invest 1994:93:2293-6).
In 1994, the therapeutic potential of GLP-1 was suggested following the observation that a single subcutaneous (s/c) dose of GLP-1 could completely normalize postprandial glucose levels in patients with non-insulin-dependent diabetes mellitus (NIDDM) (Gutniak, M.K., et al., Diabetes Care 1994:17:1039This effect was thought to be mediated both by increased insulin release and
reduction in glucagon secretion. Furthermore, an intravenous infusion of GLP-1 has been shown to delay postprandial gastric emptying in patients with NIDDM (Williams, B., et at., J. Clin Endo Metab 1996:81:327-32). Unlike suiphonylureas, the insulinotropic action of GLP-1 is dependent on plasma glucose concentration (Holz, G.G. 4th, et al., Nature 1993:361:362-5). Thus, the loss of GLP-1mediated insulin release at low plasma glucose concentration protects against severe
CONFIRMATION COPY hypoglycemia. This combination of actions gives GLP-1 unique potential therapeutic advantages over other agents currently used to treat NIDDM.
Numerous studies have shown that when given to healthy subjects, GLP-1 potently influences glycemic levels as well as insulin and glucagon concentrations (Orskov, C, Diabetologia 35:701-711, 1992; Hoist, J.J., et al., Potential of
GLP-1 in diabetes management in Glucagon III, Handbook of Experimental Pharmacology,
Lefevbre PJ, Ed. Berlin, Springer Verlag, 1996, p. 311-326), effects which are glucose dependent (Kreymann, B., et al., Lancet ii: 1300-1304, 1987; Weir,
et al., Diabetes 38:338-342, 1989). Moreover, it is also effective in patients with diabetes (Gutniak, M., N. Engl J Med 226:1316-1322, 1992; Nathan, D.M., et
Diabetes Care 15:270-276, 1992), normalizing blood glucose levels in type 2 diabetic subjects (Nauck, M.A., et al., Diabetologia 36:741-744, 1993), and improving glycemic control in type I patients (Creutzfeldt, W.O., et al.,
Diabetes
Care 19:580-586, 1996), raising the possibility of its use as a therapeutic agent.
GLP-1 is, however, metabolically unstable, having a plasma half-life (t12) of only 1-2 min in vivo. Exogenously administered GLP-1 is also rapidly degraded (Deacon, C.F., et al., Diabetes 44:1126-1131, 1995). This metabolic instability limits the therapeutic potential of native GLP-1. Hence, there is a need for GLP-1 analogues that are more active or are more metabolically stable than native
GLP-1.
Summary of the Invention
In one aspect, the present invention is directed to a compound of formula
(R2R3)-A7-A8-A9-A10-A1' -A' 2-A13_Al4_AI S_A16-A17-A' 8-A' 9-A20-A21-A22-A23A24-A25-A28-A27A28-A29-A30-A31-A32-A33-A34-A35-A36-A37-A38-A39-R'
wherein
A7 is L-His, Ura, Paa, Pta, Amp, Tma-His, des-amino-His, or deleted;
A8 is Ala, D-Ala, Aib, Acc, N-Me-Ala, N-Me-D-Ala or N-Me-Gly;
A9 is Glu, N-Me-Glu, N-Me-Asp or Asp;
All is Gly, Acc, 13-Ala or Aib;
A" is Thr or Ser;
A12 is Phe, Acc, Aic, Aib, 3-Pal, 4-Pal, 13-Nal, Cha, Trp or X'-Phe;
A13 is Thr or Ser;
A14 is Ser or Aib;
A 15 is Asp or Glu;
A16 is Val, Acc, Aib, Leu, lie, Tie, Nle, Abu, Ala or Cha;
A" is Ser or Thr;
Aib is Ser or Thr;
At9 is Tyr, Cha, Phe, 3-Pal, 4-Pal, Acc, 13-Nat or X'-Phe;
A20 is Leu, Acc, Aib, Nle, lie,, Cha, Tie, Val, Phe or X'-Phe;
A21 is Glu or Asp;
A22 is Gly, Acc, 13-Ala, Glu or Aib;
A23 is Gin, Asp, Asn or Glu;
A24 is Ala, Aib, Val, Abu, Tie or Acc;
A25 is Ala, Aib, Val, Abu, Tie, Acc, Lys, Arg, hArg, Om, HN-CH((CH2),-
C(O) or HN-CH((CH2),-X3)-C(O);
A26 is Lys, Arg, hArg, Orn, HN-CH((CH2)õN(R10R"))-C(O) or HN-CH((CH2),_X3)_
A27 is Glu Asp, Leu, Aib or Lys;
A28 is Phe, Pal, 13-Nat, X'-Phe, Aic, Acc, Aib, Cha or Trp;
A29 is Ile, Acc, Aib, Leu, Nle, Cha, Tie, Vat, Abu, Ala or Phe;
A30 is Ala, Aib or Acc;
A31 is Trp, 13-Nal, 3-Pal, 4-Pal, Phe, Acc, Aib or Cha;
A32 is Leu, Acc, Aib, Nle, lie, Cha, Tie, Phe, X'-Phe or Ala;
A33 is Val, Acc, Aib, Leu, Ile, Tie, Nie, Cha, Ala, Phe, Abu, Lys or X'-Phe;
A34 is Lys, Arg, hArg, Om, HN-CH((CH2)õN(R10R"))-C(O) or HN-CH((CH2); X3)-
A35 is Gly, 13-Ala, D-Ala, Gaba, Ava, HN-(CH2)m C(O), Aib, Acc or a D-amino acid;
A36 is L- or D-Arg, D- or L-Lys, D- or L-hArg, D- or L-Orn, HN-CH((CH2),-
C(O), HN-CH((CH2); X3)-C(O) or deleted;
A37 is Gly, 13-Ala, Gaba, Ava. Aib, Acc, Ado, Arg, Asp, Aun, Aec, HN-(CH2)m
HN-CH((CH2),, N(R10R"))-C(O), a D-amino acid, or deleted;
A3a is D- or L-Lys, D- or L-Arg, D- or L-hArg, D- or L-Om, HNCH((CH2)õN(R10R")) C(O), HN-CH((CH2); X3)-C(O) Ava, Ado, Aec or deleted;
A39is D- or L-Lys, D- or L-Arg, HN-CH((CH2)õN(R70R"))-C(O), Ava, Ado, or Aec;
X1 for each occurrence is independently selected from the group consisting of
C5)alkyl, OH and halo;
A39 may also be deleted;
R1 is OH, NH2, (C1-C30)alkoxy, or NH-X2-CH2-Z , wherein X2 is a (C,C12)hydrocarbon moiety, and Z is H, OH, CO2H or CONH2;
X4 NN-(CH2)f -CH3
-NH-C(O)-CH2 N N-(CH 2)2-NH-C(O)-R13 or -C(O)-NHR 12, wherein X4 is, independently for each occurrence, -C(O)-, -NHC(O)- or -CH2-, and wherein f is, independently for each occurrence, an integer from 1 to 29 inclusive; each of R2 and R3 is independently selected from the group consisting of H,
C30)alkyl, (C2-C30)alkenyl, phenyl(C,-C30)alkyl, naphthyl(C,-C30)alkyl, hydroxy(C1 C30)alkyl, hydroxy(C2 C30)alkenyl, hydroxyphenyl(C,-C3(,)alkyl, and hydroxynaphthyl(C1-C30)alkyl; or one of R2 and R3 is (CH3)2 N-C=N(CH3)2 (C,-
C30)acyl, (C,-C30)alkylsulfonyl, C(O)X5, , or
Y(CH2)-N \-~ N-(CH2)q CO wherein Y is H, OH or NH2; r is O to 4; q is O to 4; and X5 is (C,-C30)alkyl, (C2-C30)alkenyl, phenyl(C1-C30)alkyl, naphthyl(C,C30)alkyl, hydroxy(C1-C30)alkyl, hydroxy(C2-C30)alkenyl, hydroxyphenyl(C,-C30)alkyl or hydroxynaphthyl(C,-C30)alkyl; e is, independently for each occurrence, an integer from 1 to 4 inclusive; m is, independently for each occurrence, an integer from 5 to 24 inclusive; n is, independently for each occurrence, an integer from 1 to 5, inclusive; each of R10 and R11 is, independently for each occurrence, H, (C,-C30)alkyl,
C30)acyl, (C,-C30)alkylsulfonyl, -C((NH)(NH2)) or -C(O)-CHi-N /N-(CH2)f-CH3 and
R12 and R13 each is, independently for each occurrence, (C,-C30)alkyl;
provided that: when A' is Ura, Paa or Pta, then R2 and R3 are deleted; when R10 is (C1-C30)acyl, (C1-C30)alkylsulfonyl, -C((NH)(NH2)) or -C(O)-CH2 NN-(CH2)f CH3 then R" is H or (C1-C30)alkyl; (i) at least one amino acid of a compound of formula (I) is not the same as the native sequence of hGLP-1 (7-36, -37 or -38)NH2 or hGLP-1 (7-36, -37 or -
(ii) a compound of formula (I) is not an analogue of hGLP-1 (7-36, -37 or hGLP-1 (7-36, -37 or -38)OH wherein a single position has been substituted by
Ala; (iii) a compound of formula (I) is not (Arg28.34, Lys38)hGLP-1(7-38)-E,
alkanoyl))hGLP-1(7-36, -37 or -38)-E, (Lys34(NE-alkanoyl))hGLP-1(7-36, -37 or -
38)-E, (Lys26' -bis(NE-alkanoyl))hGLP-1(7-36, -37 or -38)-E, (Arg28, Lys34(NEalkanoyl))hGLP-1(8-36, -37 or -38)-E, (Arg26,34, Lys36(NE-alkanoyl))hGLP-1(7or -38)-E or (Arg26,34, Lys38(NE-alkanoyl))hGLP-1(7-38)-E, wherein E is -OH or
(iv) a compound of formula (I) is not Z'-hGLP-1(7-36, -37 or -38)-OH, Z'-hGLP36, -37 or -38)-NH2, wherein Z' is selected from the group consisting of: (a) (Arg26), (Arg34), (Arg26,34), (Lys38), (Arg26, Lys36), (Arg34, Lys36), (D-
(Arg36), (D-Arg36), (Arg26,34, Lys36) or (Arg26,36, LysTM);
(c) at least one of (Aib8), (D-Ala8) and (Asp9); and (d) (Tyr7), (N-acyl-His'), (N-alkyl-His'), (N-acyl-D-His') or (N-alkyl-DHis'); (v) a compound of formula (I) is not a combination of any two of the substitutions listed in groups (a) to (d); and (vi) a compound of formula (I) is not (N-Me-Ala8)hGLP-1(8-36 or -37), (Glu15)hGLP1(7-36 or -37), (Asp21)hGLP-1(7-36 or -37) or (Phe31)hGLP-1(7-36 or -37) or a pharmaceutically acceptable salt thereof.
A preferred group of compounds of the immediately foregoing compound is where A11 is Thr; A13 is Thr; A15 is Asp; A17 is Ser; A18 is Ser or Lys; A21 is Glu; A23 is
Gin or Glu; A27 is Glu, Leu, Aib or Lys; and A31 is Trp, Phe or t3-Nal; or a pharmaceutically acceptable salt thereof.
A preferred group of compounds of the immediately foregoing group of compounds is where A9 is Glu, N-Me-Glu or N-Me-Asp; A12 is Phe, Acc, 13-Nal or
Aic; A16 is Val, Acc or Aib; A19 is Tyr or 13-Nal; A20 is Leu, Acc or Cha; A24 is Ala, Aib or Acc; A25 is Ala, Aib, Acc, Lys, Arg, hArg, Orn, HN-CH((CH2),, N(R10R"))HN-CH((CH2)e X3)-C(O); A28 is Phe or 13-Nal; A29 is lie or Acc; A30 is Ala or
Aib; A32 is Leu, Acc or Cha; and A33 is Val, Lys or Acc; or a pharmaceutically acceptable salt thereof.
A preferred group of compounds of the immediately foregoing group of compounds is where AB is Ala, D-Ala, Aib, A6c, A5c, N-Me-Ala, N-Me-D-Ala or NMe-Gly; A10 is Gly; A12 is Phe, 13-Nal, A6c or A5c; A16 is Val, A6c or A5c;
A20 is Leu,
A6c, A5c or Cha; A22 is Gly, 13-Ala, Glu or Aib; A24 is Ala or Aib; A29 is
Ile, A6c or
A5c; A32 is Leu, A6c, A5c or Cha; A33 is Val, Lys, A6c or A5c; A35 is Aib, 13Ala, Ado,
A6c, A5c, D-Arg or Gly; and A37 is Gly, Aib, /3-Ala, Ado, D-Ala Ava, Asp, Aun,
Asp, D-Arg, Aec, HN-CH((CH2)õN(R10R"))-C(O) or deleted; or a pharmaceutically acceptable salt thereof.
A preferred group of compounds of the immediately foregoing group of compounds is where X4 for each occurrence is -C(O)-; and R' is OH or NH2; or a pharmaceutically acceptable salt thereof.
A preferred group of compounds of the immediately foregoing group of compounds or a pharmaceutically acceptable salt thereof is where R2 is H and
(C,-C30)alkyl, (C2-C30)alkenyl, (C,-C30)acyl, (C,-C30)alkylsulfonyl,
HO-(CH2)2 N \-2 N-(CH2)2SO2 , HO-(CH 2)2 N N-CH2 CO
H2N-(CH2)2 ~~ -CH2 COA preferred compound of the formula (I) is where AB is Ala, D-Ala, Aib, A6c,
A5c, N-Me-Ala, N-Me-D-Ala or N-Me-Gly; A'0 is Gly; A'2 is Phe, 13-Nal A6c or
A16 is Val, A6c or A5c; A20 is Leu, A6c, A5c or Cha; A22 is Gly, (3-Ala, Glu or Aib; A24 is Ala or Aib; A29 is lie, A6c or A5c; A32 is Leu, A6c, A5c or Cha; A33 is
Val, Lys, A6c or A5c; A35 is Aib, 13-Ala, Ado, A6c, A5c D-Arg or Gly; and A37 is Gly, Aib, 13-Ala,
Ado, D-Ala, Ava, Asp, Aun, D-Asp, D-Arg, Aec, HN-CH((CH2),, N(Rt0R"))-C(O) or deleted; X4 for each occurrence is -C(O)-; e for each occurrence is independently 1 or 2; R' is OH or NH2; R10 is (C1-C30)acyl, (C1-C30)alkylsulfonyl or
-C(O)-CH2 N \_~ N-(CH2)f CH3 and R'1 is H; or a pharmaceutically acceptable salt thereof.
More preferred of the immediately foregoing compounds is where R1 is (C; -C(O)-CH2 N \--/ N-(CH2)f CH3
C20)acyl, (C4-C20)alkylsulfonyl or ~ , or a pharmaceutically acceptable salt thereof.
A more preferred compound of formula (I) is where said compound is of the formula: (Aib8'35)hGLP-1(7-36)NH2, ((Na-HEPES-HiS)7, Aib6'35)hGLP-1(7-36)NH2, ((Na-HEPA-His)7, Aib8.36)hGLP-1(7-36)NH2, (Aib6, 13-Ala 35)hGLP-1(7-36)NH2, (Aib8,35, Arg26'34, Lys38(Ne-tetradecanoyl))hGLP-1(7-36)NH2, (Aib8,35, Arg26, Lys34(NE-tetradecanoyl))hGLP-1(7-36)NH2, (Aib835,37, Arg26.3.1, Lys38(Ne-tetradecanoyl))hGLP-1(7-38)NH2i (Aib8'35, Arg26.34, Lys38(NE-decanoyl))hGLP-1(7-36)NH2, (Aib835, Arg261, Lys36(NE-dodecanesulfonyl))hGLP-1(7-36)NH2, (Aib8,35, Arg26'34, Lys36(NE-(2-(4-tetradecyl-1-piperazine)-acetyl)))hGLP-1(7-
(Aib8,35, Arg26.3i, Asp38(1-(4-tetradecyl-piperazine)))hGLP-1(7-36)NH2, (Aib835, Arg26.34, Asp38(1 -tetrad ecylami no))hG LP- 1 (7-36)NH2, (Aib835, Arg26'31, Lys38(Ne-tetradecanoyl),13-A1a31)hGLP-1(7-37)-OH or (Aib8.35, Arg26,31, LyS38(NE-tetradecanoyl))hGLP-1(7-36)-OH, or a pharmaceutically acceptable salt thereof .
More preferred of the immediately foregoing group of compounds is a compound of the formula: (Aib6'35)hGLP-1(7-36)NH2, (Aib8, 13-A1a35)hGLP-1(7-36)NH2r (Aib8.35, Arg25, Lys34(NE-tetradecanoyl))hGLP-1(7-36)NH2, (Aib8'35,37, Arg26.34, Lys38(NE-tetradecanoyl))hGLP-1(7-38)NH2, (Aib8.35, Arg26.3`, Lys36(Ne-decanoyl))hGLP-1(7-36)NH2, or
(Aib8.35, Arg26.34, Lys38(NE-tetradecanoyl),(3-A1a37)hGLP-1(7-37) -OH, or a pharmaceutically acceptable salt thereof.
Another more preferred compound of formula (I) is where said compound is of the formula: (Aib8,35, A6c32)hGLP-1(7-36)NH2; (Aibe,35, GIu23)hGLP-1(7-36)NH2; (Aib8.24.35)hGLP-1(7-36)NH2; (Aib8.35, GIu23, A6c32)hGLP-1 (7-36)NH2; (Aib8, GIu23, 13-Ala 35)hGLP-1(7-36)NH2; (Aibe,35, Arg26,34)hGLP-1(7-36)NH2; (Aibe,35, Arg26,34, Lys36(N-octanoyl))hGLP-1(7-36)NH2; (Aib8.35, Arg26,34, Lys36(N`-decanoyl))hGLP-1(7-36)OH; (Aib8,35, Lys25, Arg28'34, Lys36(N`-decanoyl))hGLP-1(7-36)OH; (Aib8, Arg26'34, 1,-Ala35, Lys36(N`-Aec-decanoyl))hGLP-1(7-36)NH2i (Aib1.35,Arg26.34, Ava37, Ado38)hGLP-1(7-38)NH2; (Aib8 35,Arg26,34, Asp37, Ava38, Ado39)hGLP-1(7-39)NH2i (AIb835,Arg26,34, Aun37)hGLP-1(7-37)NH2i (Aib8,17,35,)hGLP-1(7-36)NH2; (Aib8 ,Arg26,34, /3_Ala35, D-Asp37, Ava38, Aun31)hGLP-1(7-39)NH2i (GIy8, (3-Ala 35)hGLP-1(7-36)NH2; (Sera, 13-Ala 31)hGLP-1(7-36)NH2; (Aib8, GIu22'23, /3_A1a35)hGLP-1(7-36)NH2i (GIy8, Aib35)hGLP-1(7-36)NH2; (Aib8, Lys18, f3-Ala35)hGLP-1(7-36)NH2; (Aib8, Leu27, (3-Ala 35)hGLP-1(7-36)NH2; (Aib8, Lys33, 13-Ala 35)hGLP-1(7-36)NH2; (Aib8, Lys18, Leu27, 13-Ala35)hGLP-1(7-36)NH2; (Aib8, D-Arg36 )hGLP-1 (7-36)NH2; (Aib8, 13-Ala35, D-Arg37)hGLP-1(7-37)NH2; (Aib8,27, (3-Ala 31)hGLP-1(7-36)NH2i (Aib8 27, (3-Ala35,37 Arg31)hGLP-1(7-38)NH2; (Aib1=27, (3-Ala 35,37 Arg38,39)hGLP-1(7-39)NH2i (Aib8, Lys 11.27, 13-Ala 31 )hGLP-1(7-36)NH2; (Aib8, Lys27, (3-Ala 35)hGLP-1(7-36)NH2;
(Aib8, 13-Ala35, Arg38)hGLP-1(7-38)NH2; (Aib8, Arg26.34, 13-Ala35, )hGLP-1 (7-36)NH2; (Aib8, D-Arg35 )hGLP-1 (7-36)NH2; (Aib8, 13-Ala35, Arg37)hGLP-1(7-37)NH2; (Aib8, Phe31, 13-Ala35)hGLP-1(7-36)NH2; (Aib8'31, Phe31)hGLP-1(7-36)NH2i (Aib8.35, Nal31)hGLP-1(7-36)NH2; (Aib8.35, Nal28.31)hGLP-1(7-36)NH2; (Aib835 Arg26'34, Na131 )hGLP-1 (7-36)NH2; (Aib8.35, Arg26.34, Phe31)hGLP-1(7-36)NH2i (Aib835, Na119=31)hGLP-1(7-36)NH2i (Aib835, Na112.31)hGLP-1(7-36)NH2; (Aib8'35, Lys36(N-decanoyl))hGLP-1(7-36) NH2i (Aib8,35, Arg34, Lys28(N`-decanoyl))hGLP-1(7-36)NH2; (Aib8.35, Arg26'34, Lys38(N`-dodecanoyl))hGLP-1(7-36)NH2; (Aib8,B-Ala35, Ser37(O-decanoyl))hGLP1(7-37)-NH2; (Aib8'27, 13-Ala35,37, Arg38, Lys39(N`-octanoyl))hGLP-1(7-39)NH2; (Aib8, Arg26'34, 1_Ala35, Lys37(N`-octanoyl))hGLP-1(7-37)NH2; (Aib8, Arg26,3113_Ala35, Lys37(NE-decanoyl))hGLP-1(7-37)NH2; or (Aib8, Arg26.34, f3_Ala35, Lys37(NE-tetradecanoyl))hGLP-1(7-37)NH2; or a pharmaceutically acceptable salt thereof.
Another more preferred compound of formula (I) is each of the compounds that are specifically enumerated hereinbelow in the Examples section of the present disclosure, or a pharmaceutically acceptable salt thereof.
In another aspect, the present invention provides a pharmaceutical composition comprising an effective amount of a compound of formula (I) as defined hereinabove or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier or diluent.
In yet another aspect, the present invention provides a method of eliciting an agonist effect from a GLP-1 receptor in a subject in need thereof which comprises administering to said subject an effective amount of a compound of formula (1) as defined hereinabove or a pharmaceutically acceptable salt thereof.
In a further aspect, the present invention provides a method of treating a disease selected from the group consisting of Type I diabetes, Type II diabetes,
obesity, glucagonomas, secretory disorders of the airway, metabolic disorder, arthritis, osteoporosis, central nervous system disease, restenosis, neurodegenerative disease, renal failure, congestive heart failure, nephrotic syndrome, cirrhosis, pulmonary edema, hypertension, and disorders wherein the reduction of food intake is desired, in a subject in need thereof which comprises administering to said subject an effective amount of a compound of formula (I)
defined hereinabove or a pharmaceutically acceptable salt thereof. A preferred method of the immediately foregoing method is where the disease being treated
Type I diabetes or Type II diabetes.
With the exception of the N-terminal amino acid, all abbreviations (e.g. Ala) of amino acids in this disclosure stand for the structure of -NH-CH(R)-CO-, wherein
R is the side chain of an amino acid (e.g., CH3 for Ala). For the N-terminal amino acid, the abbreviation stands for the structure of (R2R3)-N-CH(R)-CO-, wherein
a side chain of an amino acid and R2 and R3 are as defined above, except when
is Ura, Paa or Pta, in which case R2 and R3 are not present since Ura, Paa and
Pta are considered here as des-amino amino acids. Amp, 13-Nal, NIe, Cha, 3-Pal, 4Pal and Aib are the abbreviations of the following a-amino acids: 4-aminophenylalanine, 13-(2-naphthyl)alanine, norleucine, cyclohexylalanine, 13-(3pyridinyl)alanine, 13-(4-pyridinyl)alanine and a-aminoisobutyric acid, respectively.
Other amino acid definitions are: Ura is urocanic acid; Pta is (4-pyridylthio) acetic acid; Paa is trans-3-(3-pyridyl) acrylic acid; Tma-His is N,Ntetramethylamidinohistidine; N-Me-Ala is N-methyl-alanine; N-Me-Gly is N-methyl-glycine; N-MeGlu is
N-methyl-glutamic acid; Tie is tert-butylglycine; Abu is a-aminobutyric acid;
Tba is tert-butylalanine; Orn is ornithine; Aib is a-aminoisobutyric acid; /3-Ala is 13-alanine;
Gaba is 7-aminobutyric acid; Ava is 5-aminovaleric acid; Ado is 12aminododecanoic acid, Aic is 2-aminoindane-2-carboxylic acid; Aun is 11aminoundecanoic acid; and Aec is 4-(2-aminoethyl)-1-carboxymethyl-piperazine,
represented by the structure:
What is meant by Acc is an amino acid selected from the group of 1-amino1-cyclopropanecarboxylic acid (A3c); 1-amino-1-cyclobutanecarboxylic acid
1 -amino- 1 -cyclopentanecarboxylic acid (A5c); 1 -amino- 1 cyclohexanecarboxylic acid (A6c); 1-amino-1-cycloheptanecarboxylic acid (A7c); 1-amino-1cyclooctanecarboxylic acid (A8c); and 1-amino-l-cyclononanecarboxylic acid
In the above formula, hydroxyalkyl, hydroxyphenylalkyl, and hydroxynaphthylalkyl may contain 1-4 hydroxy substituents. COX5 stands for -C=O=X5. Examples of C=O.X5 include, but are not limited to, acetyl and phenylpropionyl.
What is meant by Lys(NE-alkanoyl) is represented by the following structure:
H 0 . What is meant by Lys(NE-alkylsulfonyl) is represented by the following structure: H 0 . What is meant by Lys(NE-(2-(4-alkyl-1-piperazine)-acetyl)) is represented by the following structure: H 0 . What is meant by
Asp(1-(4-alkyl-piperazine)) is represented by the following structure: H 0 . What is meant by Asp(1-alkylamino)
is represented by the following structure: H 0 What is meant by Lys(NE-Aec-alkanoyl) is represented by the structure:
NPN Nom`/N CH3
H 0 The variable n in the foregoing structures is 1-30. What is meant by Lys (Ns-ace-alkanoyl) is represented by the structure:
The full names for other abbreviations used herein are as follows: Boc for tbutyloxycarbonyl, HF for hydrogen fluoride, Fm for formyl, Xan for xanthyl,
BzI for benzyl, Tos for tosyl, DNP for 2,4-dinitrophenyl, DMF for dimethylformamide,
DCM for dichloromethane, HBTU for 2-(1H-Benzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate, DIEA for diisopropylethylamine, HOAc for acetic acid, TFA for trifluoroacetic acid, 2CIZ for 2-chlorobenzyloxycarbonyl, 2BrZ for 2bromobenzyloxycarbonyl, OcHex for O-cyclohexyl, Fmoc for 9fluorenylmethoxycarbonyl, HOBt for N-hydroxybenzotriazole and PAM resin for 4hyd roxymethylphenylacetamidomethyl resin.
The term "halo" encompasses fluoro, chloro, bromo and iodo.
The term "(C,-C30)hydrocarbon moiety" encompasses alkyl, alkenyl and alkynyl, and in the case of alkenyl and alkynyl there are C2-C30.
A peptide of this invention is also denoted herein by another format, e.g., (A5c')hGLP-1(7-36)NH2, with the substituted amino acids from the natural sequence placed between the first set of parentheses (e.g., A5c' for Ala' in hGLP1). The abbreviation GLP-1 means glucagon-like peptide-1; hGLP-1 means human glucagon-like peptide-1. The numbers between the parentheses refer to the number of amino acids present in the peptide (e.g., hGLP-1(7-36) is amino acids 7 through 36 of the peptide sequence for human GLP-1). The sequence for hGLP1(7-37) is listed in Mojsov, S., Int. J. Peptide Protein Res., 40, 1992, pp. 333-342. The designation "NH2" in hGLP-1 (7-36)NH2 indicates that the C-terminus of the peptide is amidated. hGLP-1(7-36) means that the C-terminus is the free acid. In hGLP-1(7residues in positions 37 and 38 are Gly and Arg, respectively.
This invention also provides a composition comprising a compound as described above or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent.
This invention also provides the use of a compound as described above or a pharmaceutically acceptable salt thereof, for preparation of a medicament.
This invention also provides the use of a compound or pharmaceutical composition as described above for eliciting an agonist effect from a GLP-1 receptor.
This invention also provides the use of a compound as described above for treating a disease. The disease may be selected from the group consisting of Type I diabetes,
Type II diabetes, obesity, glucagonomas, secretory disorders of the airway, arthritis, osteoporosis, central nervous system disease, restenosis and neurodegenerative disease.
Detailed Description
The peptides of this invention can be prepared by standard solid phase peptide synthesis. See, e.g., Stewart, J.M., et al., Solid Phase Synthesis (Pierce
Chemical Co., 2d ed. 1984). The substituents R2 and R3 of the above generic formula may be attached to the free amine of the N-terminal amino acid by standard methods known in the art. For example, alkyl groups, e.g., (C,C30)alkyl, may be attached using reductive alkylation. Hydroxyalkyl groups, e.g., (C,C30)hydroxyalkyl, may also be attached using reductive alkylation wherein the free hydroxy group is protected with a t-butyl ester. Acyl groups, e.g., COE', may
attached by coupling the free acid, e.g., E'COOH, to the free amine of the Nterminal amino acid by mixing the completed resin with 3 molar equivalents of both the free acid and diisopropylcarbodiimide in methylene chloride for one hour.
If the free acid contains a free hydroxy group, e.g., p-hydroxyphenylpropionic acid, then the coupling should be performed with an additional 3 molar equivalents of
HOBT.
When R' is NH-X2-CH2-CONH2, (i.e., Z =CONH2), the synthesis of the peptide starts with BocHN-X2-CH2-COON which is coupled to the MBHA resin. If
R' is NH-X2-CH2-COON, (i.e., Z =COOH) the synthesis of the peptide starts with
Boc-HN-X2-CH2-COON which is coupled to PAM resin. For this particular step, 4 molar equivalents of Boc-HN-X2-COOH, HBTU and HOBt and 10 molar equivalents of DIEA are used. The coupling time is about 8 hours.
The protected amino acid 1-(N-tert-butoxycarbonyl-amino)-1-cyclohexanecarboxylic acid (Boc-A6c-OH) was synthesized as follows. 19.1 g (0.133 mol) of
amino-1-cyclohexanecarboxylic acid (Acros Organics, Fisher Scientific,
Pittsburgh,
PA) was dissolved in 2d0 ml of dioxane and 100 ml of water. To it was added 67 ml of 2N NaOH. The solution was cooled in an ice-water bath. 32.0 g (0.147 mol) of di-tert-butyl-dicarbonate was added to this solution. The reaction mixture was stirred overnight at room temperature. Dioxane was then removed under reduced pressure. 200 ml of ethyl acetate was added to the remaining aqueous solution.
The mixture was cooled in an ice-water bath. The pH of the aqueous layer was adjusted to about 3 by adding 4N HCI. The organic layer was separated. The aqueous layer was extracted with ethyl acetate (1 x 100 ml). The two organic layers were combined and washed with water (2 x 150 ml), dried over anhydrous
MgSO4, filtered, and concentrated to dryness under reduced pressure. The residue was recrystallized in ethyl acetate/hexanes. 9.2 g of the pure product was obtained. 29% yield.
Boc-A5c-OH was synthesized in an analogous manner to that of Boc-A6cOH. Other protected Acc amino acids can be prepared in an analogous manner by a person of ordinary skill in the art as enabled by the teachings herein.
In the synthesis of a GLP-1 analogue of this invention containing A5c, A6c and/or Aib, the coupling time is 2 hrs. for these residues and the residue immediately following them. For the synthesis of (Tma-His7)hGLP-1(7-36)NH2,
HBTU (2 mmol) and DIEA (1.0 ml) in 4 ml DMF are used to react with the Nterminal free amine of the peptide-resin in the last coupling reaction; the coupling time is about 2 hours.
The substituents R2 and R3 of the above generic formula can be attached to the free amine of the N-terminal amino acid by standard methods known in the art.
For example, alkyl groups, e.g., (C1-C30)alkyl, can be attached using reductive alkylation. Hydroxyalkyl groups, e.g., (C,-C30)hydroxyalkyl, can also be attached using reductive alkylation wherein the free hydroxy group is protected with a t-butyl ester. Acyl groups, e.g., COX', can be attached by coupling the free acid,
X'COOH, to the free amine of the N-terminal amino acid by mixing the completed resin with 3 molar equivalents of both the free acid and diisopropylcarbodiimide in methylene chloride for about one hour. If the free acid contains a free hydroxy group, e.g., p-hydroxyphenylpropionic acid, then the coupling should be performed with an additional 3 molar equivalents of HOBT.
A compound of the present invention can be tested for activity as a GLP-1 binding compound according to the following procedure.
Cell Culture:
RIN 5F rat insulinoma cells (ATCC-# CRL-2058, American Type Culture
Collection, Manassas, VA), expressing the GLP-1 receptor, were cultured in
Dulbecco's modified Eagle's medium (DMEM) containing 10% fetal calf serum, and maintained at about 37 C in a humidifed atmosphere of 5% CO2/95% air.
Radioligand Binding:
Membranes were prepared for radioligand binding studies by homogenization of the RIN cells in 20 ml of ice-cold 50 mM Tris-HCI with a
Brinkman Polytron* (Westbury, NY) (setting 6, 15 sec). The homogenates were washed twice by centrifugation (39,000 g / 10 min), and the final pellets were resuspended in 50 mM Tris-HCI, containing 2.5 mM MgCl2, 0.1 mg/ml bacitracin (Sigma Chemical, St. Louis, MO), and 0.1% BSA. For assay, aliquots (0.4 mi) were incubated with 0.05 nM (1231)GLP-1(7-36) (-2200 Ci/mmol, New England
Nuclear, Boston, MA), with and without 0.05 ml of unlabeled competing test peptides. After a 100 min incubation (25 C), the bound (1251)GLP-1(7-36) was separated from the free by rapid filtration through GF/C filters (Brandel, 1o Gaithersburg, MD), which had been previously soaked in 0.5% polyethyleneimine.
The filters were then washed three times with 5 ml aliquots of ice-cold 50 mM
TrisHCI, and the bound radioactivity trapped on the filters was counted by gamma spectrometry (Wallac LKB, Gaithersburg, MD). Specific binding was defined as the total (1251)GLP-1(7-36) bound minus that bound in the presence of 1000 nM
GLP1 (7-36) (Bachem, Torrence, CA).
The peptides of this invention can be provided in the form of pharmaceutically acceptable salts. Examples of such salts include, but are not limited to, those formed with organic acids (e.g., acetic, lactic, maleic, citric, malic, ascorbic, succinic, benzoic, methanesulfonic, toluenesulfonic, or pamoic acid), inorganic acids (e.g., hydrochloric acid, sulfuric acid, or phosphoric acid), and polymeric acids (e.g., tannic acid, carboxymethyl cellulose, polylactic, potyglycotic, or copolymers of polylactic-glycolic acids). A typical method of making a salt
peptide of the present invention is well known, in the art and can be accomplished by standard methods of salt exchange. Accordingly, the TFA salt of a peptide of the present invention (the TFA salt results from the purification of the peptide by using preparative HPLC, eluting with TFA containing buffer solutions) can be converted into another salt, such as an acetate salt by dissolving the peptide in a small amount of 0.25 N acetic acid aqueous solution. The resulting solution is applied to a semi-prep HPLC column (Zorbax, 300 SB, C-8). The column is eluted with (1)
OA N ammonium acetate aqueous solution for 0.5 hrs., (2) 0.25N acetic acid aqueous solution for 0.5 hrs. and (3) a linear gradient (20% to 100% of solution B over 30 min.) at a flow rate of 4 ml/min (solution A is 0.25N acetic acid aqueous solution; solution .B is 0.25N acetic acid in acetonitrile/water, 80:20). The fractions containing the peptide are collected and lyophilized to dryness. * Trademark
As is well known to those skilled in the art, the known and potential uses of
GLP-1 is varied and multitudinous (See, Todd, J.F., et at, Clinical Science,
95, pp. 325-329; and Todd, J.F. et al., European Journal of Clinical
Investigation, 1997, 27, pp.533-536). Thus, the administration of the compounds of this invention for purposes of eliciting an agonist effect can have the same effects and uses
GLP-1 itself. These varied uses of GLP-1 may be summarized as follows, treatment of: Type I diabetes, Type II diabetes, obesity, glucagonomas, secretory disorders of the airway, metabolic disorder, arthritis, osteoporosis, central nervous system diseases, restenosis, neurodegenerative diseases, renal failure, congestive heart failure, nephrotic syndrome, cirrhosis, pulmonary edema, hypertension, and disorders wherein the reduction of food intake is desired. GLP-1 analogues of the present invention that elicit an antagonist effect from a subject can be used for treating the following: hypoglycemia and malabsorption syndrome associated with gastroectomy or small bowel resection.
Accordingly, the present invention includes within its scope pharmaceutical compositions comprising, as an active ingredient, at least one of the compounds of formula (I) in association with a pharmaceutically acceptable carrier.
The dosage of active ingredient in the compositions of this invention may be varied; however, it is necessary that the amount of the active ingredient be such that a suitable dosage form is obtained. The selected dosage depends upon the desired therapeutic effect, on the route of administration, and on the duration of the treatment. In general, an effective dosage for the activities of this invention is in the range of 1x10-Ito 200 mg/kg/day, preferably 1x10-4 to 100 mg/kg/day, which can
administered as a single dose or divided into multiple doses.
The compounds of this invention can be administered by oral, parenteral (e.g., intramuscular, intraperitoneal, intravenous or subcutaneous injection,
implant), nasal, vaginal, rectal, sublingual or topical routes of administration and can be formulated with pharmaceutically acceptable carriers to provide dosage forms appropriate for each route of administration.
Solid dosage forms for oral administration include capsules, tablets, pills, powders and granules. In such solid dosage forms, the active compound is admixed with at least one inert pharmaceutically acceptable carrier such as sucrose, lactose, or starch. Such dosage forms can also comprise, as is normal practice, additional substances other than such inert diluents, e.g., lubricating agents such as magnesium stearate. In the case of capsules, tablets and pills, the dosage forms may also comprise buffering agents. Tablets and pills can additionally be prepared with enteric coatings.
Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups, the elixirs containing inert diluents commonly used in the art, such as water. Besides such inert diluents, compositions can also include adjuvants, such as wetting agents, emulsifying and suspending agents, and sweetening, flavoring and perfuming agents.
Preparations according to this invention for parenteral administration include sterile aqueous or non-aqueous solutions, suspensions, or emulsions. Examples
non-aqueous solvents or vehicles are propylene glycol, polyethylene glycol, vegetable oils, such as olive oil and corn oil, gelatin, and injectable organic esters such as e.hyl oleate. Such dosage forms may also contain adjuvants such as preserving, wetting, emulsifying, and dispersing agents. They may be sterilized by, for example, filtration through a bacteria-retaining filter, by incorporating sterilizing agents into the compositions, by irradiating the compositions, or by heating the compositions. They can also be manufactured in the form of sterile solid compositions which can be dissolved in sterile water, or some other sterile injectable medium immediately before use.
Compositions for rectal or vaginal administration are preferably suppositories which may contain, in addition to the active substance,' excipients such as coca butter or a suppository wax.
Compositions for nasal or sublingual administration are also prepared with standard excipients well known in the art.
Further, a compound of this invention can be administered in a sustained release composition such as those described in the following patents and patent applications. U.S. Patent No. 5,672,659 teaches sustained release compositions comprising a bioactive''agent and a polyester. U.S. Patent No. 5,595,760 teaches sustained release compositions comprising a bioactive agent in a gelable form.
International Patent Publication No. WO 96/39160, teaches polymeric sustained release compositions comprising a bioactive agent and chitosan. International
Patent
Publication No. WO 98/20044,teaches sustained release compositions comprising
bioactive agent and cyclodextrin. International Patent Publication No. WO
teaches absorbable sustained release compositions of a bioactive agent.
International Patent Publication No. WO 00/04916, teaches a process for making microparticles comprising a therapeutic agent such as a peptide in an oil-inwater process. International Patent Publication No. WO 00/09166, teaches complexes comprising a therapeutic agent such as a peptide and a phosphorylated polymer. International Patent Publication No. WO 00/25826, teaches complexes comprising a therapeutic agent such as a peptide and a polymer bearing a non-polymerizable lactone.
Unless defined otherwise, all technical and scientific terms used herein have. the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.
The following examples describe synthetic methods for making a peptide of this invention, which methods are well-known to those skilled in the art.
Other methods are also known to those skilled in the art. The examples are provided for the purpose of illustration and is not meant to limit the scope of the present invention in any manner.
Boc-/3AIa-OH, Boc-D-Arg(Tos)-OH and Boc-D-Asp(OcHex) were purchased from Nova Biochem, San Diego, California. Boc-Aun-OH was purchased from
Bachem, King of Prussia, PA. Boc-Ava-OH and Boc-Ado-OH were purchased from
Chem-Impex International, Wood Dale, IL. Boc-Nal-OH was purchased from
Synthetech, Inc. Albany, OR.
Example 1 (Aib =35)hGLP-1(7-36)NH2
The title peptide was synthesized on an Applied Biosystems (Foster City,
CA) model 430A peptide synthesizer which was modified to do accelerated Bocchemistry solid phase peptide synthesis. See Schnolzer, et al., Int. J.
Peptide
Protein Res., 90:180 (1'992). 4-methylbenzhydrylamine (MBHA) resin (Peninsula,
Belmont, CA) with the substitution of 0.91 mmol/g was used. The Boc amino acids (Bachem, CA, Torrance, CA; Nova Biochem., LaJolla, CA) were used with the following side chain protection: Boc-Ala-OH, Boc-Arg(Tos)-OH, Boc-Asp(OcHex)OH, Boc-Tyr(2BrZ)-OH, Boc-His(DNP)-OH, Boc-VaI-OH, Boc-Leu-OH, Boc-GlyOH, Boc-Gin-OH, Boc-Ile-OH, Boc-Lys(2CIZ)-OH, Boc-Thr(Bzl)-OH, Boc-Ser(BzI)OH, Boc-Phe-OH, Boc-Aib-OH, Boc-Glu(OcHex)-OH and Boc-Trp(Fm)-OH. The synthesis was carried out on a 0.20 mmol scale. The Boc groups were removed by treatment with 100% TFA for 2 x 1 min. Boc amino acids (2.5 mmol) were preactivated with HBTU (2.0 mmol) and DIEA (1.0 mL) in 4 mL of DMF and were coupled without prior neutralization of the peptide-resin TFA salt. Coupling times were 5 min. except for the Boc-Aib-OH residues and the following residues, BocLys(2CIZ)-OH and Boc-His(DNP)-OH wherein the coupling times were 2 hours.
At the end of the assembly of the peptide chain, the resin was treated with a solution of 20% mercaptoethanol/10% DIEA in DMF for 2 x 30 min. to remove the
DNP group on the His side chain. The N-terminal Boc group was then removed by treatment with 100% TFA for 2 x 2 min. After neutralization of the peptideresin with 10% DIEA in DMF (1 x 1 min), the formyl group on the side chain of Trp was removed by treatment with a solution of 15% ethanolamine/ 15% water/ 70% DMF for 2 x 30 min. The peptide-resin was washed with DMF and DCM and dried under reduced pressure. The final cleavage was done by stirring the peptide-resin in
mL of HF containing 1 mL of anisole and dithiothreitol (24 mg) at 0 C for 75 min.
HF was removed by a flow of nitrogen. The residue was washed with ether (6 x
mL) and extracted with 4N HOAc (6 x 10 mL).
The peptide mixture in the aqueous extract was purified on reverse-phase preparative high pressure liquid chromatography (HPLC) using a reverse phase
VYDAC C18 column (Nest Group, Southborough, MA). The column was eluted with a linear gradient (20% to 50% of solution B over 105 min.) at a flow rate
mL/min (Solution A = water containing 0.1% TFA; Solution B = acetonitrile containing 0.1 % of TFA). Fractions were collected and checked on analytical
HPLC. Those containing pure product were combined and lyophilized to dryness. 135 mg of a white solid was obtained. Purity was 98.6% based on analytical
HPLC analysis. Electro-spray mass spectrometer (MS(ES))S analysis gave the molecular weight at 3339.7 (in agreement with the calculated molecular weight of
Example 2 ((N -HEPES-His)', Aib',35)hGLP-1(7-36)NH2
The title compound (HEPES is (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid)) can be synthesized as follows: after assembly of the peptide (Aib8=35)hGLP-1(7-36)NH2 on MBHA resin (0.20 mmol) according to the procedure of Example 1, the peptide-resin is treated with 100% TFA (2 x 2 min.) and washed with DMF and DCM. The resin is then neutralized with 10% DIEA in DMF for 2 min.
After washing with DMF and DCM, the resin is treated with 0.23 mmol of 2chloro1-ethanesulfonyl chloride and 0.7 mmol of DIEA in DMF for about 1 hour. The resin is washed with DMF and DCM and treated with 1.2 mmol of 2hydroxyethylpiperazine for about 2 hours. The resin is washed with DMF and DCM and treated with different reagents ((1) 20% mercaptoethanol / 10% DIEA in DMF and (2) 15% ethanolamine / 15% water / 70% DMF) to remove the DNP group on the His side chain and formyl group on the Trp side chain as described above before the final HF cleavage of the peptide from the resin.
Example 3 ((Na-HEPA-His)', Aibe.35)hGLP-1 (7-36)NH2
The title compound (HEPA is (4-(2-hydroxyethyl)-1-piperazineacetyl)) can be made substantially according to the procedure described in Example 2 for making ((Na-HEPES-His)', Aib8'35)hGLP-1(7-36)NH2 except that 2-bromoacetic anhydride is used in place of 2-chloro-l-ethanesulfonyl chloride.
Example 4 (Aib',13-Ala35)hGLP-1(7-36)NH2
The title compound was synthesized substantially according to the procedure described for Example 1 using the appropriate protected amino acids.
MS (ES) gave the molecular weight at 3325.7, calculated MW = 3325.8, purity = 99%, yield = 85 mg.
The synthesis of other compounds of the present invention can be accomplished in substantially the same manner as the procedure described for the synthesis of (Aib8-35)hGLP-1(7-36)NH2 in Example 1 above, but using the appropriate protected amino acids depending on the desired peptide.
Example 5 (Aib8'35, Arg26=34, Lys38(NE-tetradecanoyl))hGLP-1(7-36)NH2
The Boc amino acids used were the same as those in the synthesis of (Aib8'35)hGLP-1(7-36)NH2 described in Example 1 except that Fmoc-Lys(Boc)-OH was used in this example. The first amino acid residue was coupled to the resin manually on a shaker. 2.5 mmol of Fmoc-Lys(Boc)-OH was dissolved in 4 mL of 0.5N HBTU in DMF. To the solution was added 1 mL of DIEA. The mixture was shaken for about 2 min. To the solution was then added 0.2 mmol of MBHA resin (substitution = 0.91 mmol/g). The mixture was shaken for about 1 hr. The resin was washed with DMF and treated with 100% TFA for 2x2 min to remove the Boc protecting group. The resin was washed with DMF. Myristic acid (2.5 mmol) was pre-activated with HBTU (2.0 mmol) and DIEA (1.0 mL) in 4 mL of DMF for 2 min and was coupled to the Fmoc-Lys-resin. The coupling time was about 1 hr. The resin was washed with DMF and treated with 25% piperidine in DMF for 2x20 min to remove the Fmoc protecting group. The resin was washed with DMF and transferred to the reaction vessel of the peptide synthesizer. The following steps synthesis and purification procedures for the peptide were the same as those in the synthesis of (Aib8.35)hGLP-1(7-36)NH2 in Example 1. 43.1 mg of the title compound were obtained as a white solid. Purity was 98% based on analytical HPLC analysis. 1o Electro-spray mass spectrometer analysis gave the molecular weight at
agreement with the calculated molecular weight 3578.7.
Examples 6-8
Examples 6-8 were synthesized substantially according to the procedure described for Example 5 using the appropriate protected amino acid and the appropriate acid in place of the Myristic acid used in Example 5.
Example 6: (Aibe.35, Arg26, Lys34(NE-tetradecanoyl))hGLP-1(7-36)NH2; Yield =
mg; MS(ES) = 3577.2, Calculated MW = 3578.7; Purity 96%.
Example 7: (Aib8,35.37, Arg26.34, Lys38(NE-tetradecanoyl))hGLP-1(7-38)NH2;
Yield = 63.3 mg; MS(ES) = 3818.7; Calculated MW = 3819.5; Purity 96%.
Example 8: (Aib835, Arg26,34, Lys36(NE-decanoyl))hGLP-1(7-36)NH2; Yield = 57.4
MS(ES) = 3521.5; Calculated MW = 3522.7; Purity 98%; Acid = decanoic acid.
The syntheses of other compounds of the present invention containing
Lys(NE-alkanoyl) residue can be carried out in an analogous manner to the procedure described for Example 5, (Aib8,35, Arg26.34, Lys36(NEtetradecanoyl))hGLP 1(7-36)NH2. Fmoc-Lys(Boc)-OH amino acid is used for the residue of Lys(NEalkanoyl) in the peptide, while Boc-Lys(2CIZ)-OH amino acid is used for the residue of Lys. If the Lys(NE-alkanoyl) residue is not at the C-terminus, the peptide fragment immediately prior to the Lys(NE-alkanoyl) residue is assembled on the resin on the peptide synthesizer first. The appropriate acid corresponding to the desired alkanoyl can be purchased from Aldrich Chemical Co., Inc. Milwaukee, WI, USA, e.g., octanoic acid, decanoic acid, lauric acid and palmitic acid.
Example 9 (Aib8.35, Arg26'34, Lys36(NE-dodecanesulfonyl))hGLP-1(7-36)NH2
The Boc amino acids to be used in this synthesis are the same as those used in the synthesis of Example 5. The first amino acid residue is coupled to the resin manually on a shaker. 2.5 mmol of Fmoc-Lys(Boc)-OH is dissolved in 4 mL
0.5N HBTU in DMF. To the solution is added 1 mL of DIEA. The mixture is shaken for about 2 min. To the solution is then added 0.2 mmol of MBHA resin(substitution = 0.91 mmol/g). The mixture is shaken for about 1 hr. The resin is washed with
DMF and treated with 100% TFA for 2x2 min to remove the Boc protecting group.
The resin is washed with DMF and to it is added 0.25 mmol of 1dodecanesulfonyl chloride in 4 mL of DMF and 1 mL of DIEA. The mixture is shaken for about 2 hrs.
The resin is washed with DMF and treated with 25% piperidine in DMF for 2 x 20 min to remove the Fmoc protecting group. The resin is washed with DMF and transferred to the reaction vessel of the peptide synthesizer. The synthesis of the rest of the peptide and purification procedures are the same as those described in
Example 1.
The syntheses of other compounds of the present invention containing
Lys(NE-alkylsulfonyl) residue can be carried out in an analogous manner to the procedure described in Example 9. Fmoc-Lys(Boc)-OH amino acid is used for the residue of Lys(NE-alkylsulfonyl) in the peptide, while Boc-Lys(2CIZ)-OH amino acid is used for the residue of Lys. If the Lys(NE-alkylsulfonyl) residue is not at the Cterminus, the peptide fragment immediately prior to the Lys(NE-alkylsulfonyl) residue is assembled on the resin on the peptide synthesizer first. The appropriate alkylsulfonyl chloride can be obtained from Lancaster Synthesis Inc., Windham,
USA, e.g., 1-octanesulfonyl chloride, 1-decanesulfonyl chloride, 1dodecanesulfonyl chloride, 1-hexadecanesulfonyl chloride and 1octadecylsulfonyl chloride.
Example 10 (A1b835, Arg26,3`', Lys36(NE-(2-(4-tetradecyl-l -piperazine)-acetyl)))hGLP-1(7The Boc amino acids to be used for this example are the same as those used in the synthesis of Example 5. The first amino acid residue is coupled to the resin manually on a shaker. 2.5 mmol of Fmoc-Lys(Boc)-OH is dissolved in 4 mL
0.5N HBTU in DMF. To the solution is added I mL of DIEA. The mixture is shaken for about 2 min. To the solution is then added 0.2 mmol of MBHA (substitution
0.91 mmol/g) resin. The mixture is shaken for about 1 hr. The resin is washed with
DMF and treated with 100% TFA for 2x2 min to remove the Boc protecting group.
The resin is washed with DMF. The 2-bromoacetic acid (2.5 mmol) is preactivated with HBTU (2.0 mmol) and DIEA (1 mL) in 4 mL of DMF for about 2 min and is added to the resin. The mixture is shaken for about 10 min and washed with
DMF.
The resin is then treated with 1.2 mmol of piperazine in 4 mL of DMF for about
hrs. The resin is washed with DMF and treated with 2 mmol of 1-iodotetradecane for about 4 hrs. After washing with DMF, the resin is treated with 3 mmol of acetic anhydride and I mL of DIEA in 4 mL of DMF for about 0.5 hr. The resin is washed with DMF and treated with 25% piperidine in DMF for 2x20 min. The resin is washed with DMF and transferred to the reaction vessel of the peptide synthesizer to continue the synthesis. The remaining synthesis and purification procedures for the peptide are the same as the procedures described for Example 1.
The syntheses of other compounds of the present invention containing
Lys(NE-(2-(4-alkyl-1-piperazine)-acetyl)) residue are carried out in an analogous manner as the procedure described for the synthesis of Example 10. FmocLys(Boc)-OH amino acid is used for the residue of Lys(NE-(2-(4-alkyl-1piperazine)acetyl)) in the peptide, while Boc-Lys(2CIZ)-OH amino acid is used for the residue of Lys. The corresponding iodoalkane is used for the residue of Lys(NE-(2-(4alkyl1-piperazine)-acetyl)) during the alkylation step. If the Lys(NE-(2-(4-alkyl-1piperazine)-acetyl)) residue is not at the C-terminus, the peptide fragment immediately prior to the Lys(NE-(2-(4-alkyl-1-piperazine)-acetyl)) residue is assembled on the resin on the peptide synthesizer first.
Example 11 (Aib8,35, Arg26,34, Asp36(1-(4-tetradecyl-piperazine)))hGLP-1(7-36)NH2
The Boc amino acids to be used in this example are the same as the amino acids used in synthesis of Example 5 except Fmoc-Asp(O-tBu)-OH is used at position 36. The first amino acid residue is coupled to the resin manually on
shaker. 2.5 mmol of Fmoc-Asp(O-tBu)-OH is dissolved in 4 mL of 0.5N HBTU in
DMF. To the solution is added 1 mL of DIEA. The mixture is shaken for about 2 min. To the solution is then added 0.2 mmol of MBHA (substitution = 0.91 mmol/g) resin. The mixture is shaken for about 1 hr. The resin is washed with DMF and treated with 100% TFA for 2x15 min to remove the tBu protecting group. The resin is washed with DMF and is treated with HBTU (0.6 mmol) and DIEA (1 mL) in 4 mL of DMF for about 15 min. 0.6 mmol of piperazine is added to the reaction mixture and the mixture is shaken for about 1 hr. The resin is washed with DMF and treated with 3 mmol of 1-iodotetradecane for about 4 hrs. After washing with DMF, the resin is treated with 3 mmol of acetic anhydride and 1 mL of DIEA in 4 mL of
DMF for about 0.5 hr. The resin is washed with DMF and treated with 25% piperidine
DMF for 2x20 min to remove the Fmoc protecting group. The resin is washed with
DMF and transferred to the reaction vessel of the peptide synthesizer to continue the synthesis. The remaining synthesis and purification procedures for the peptide are the same as those for the synthesis of Example 1.
The syntheses of other compounds of the present invention comprising
Asp(1-(4-alkylpiperazine)) or Glu(1-(4-alkylpiperazine)) residue are carried out in an analogous manner as the procedure described for the synthesis of Example 11.
Fmoc-Asp(O-tBu)-OH or Fmoc-Glu(O-tBu)-OH amino acid is used for the residue of Asp(1-(4-alkylpiperazine)) or GIu(1-(4-alkylpiperazine)) in the peptide, while Boc Asp(OcHex)-OH or Boc-GIu(OcHex)-OH amino acid is used for the residue of Asp or Glu. The corresponding iodoalkane is used for the residue of Lys(NE-(2-(4alkyl1-piperazine)-acetyl)) during the alkylation step. If the Asp(1-(4alkylpiperazine)) or
Giu(1-(4-alkylpiperazine)) residue is not at the C-terminus, the peptide fragment immediately prior to the Asp(1-(4-alkylpiperazine)) or Glu(1-(4alkylpiperazine)) residue is assembled on the resin on the peptide synthesizer first.
Example 12 (AibB'35, Arg26.34, Asp36(1 -tetradecylamino))hGLP-1 (7-36)NH2
The Boc amino acids to be used for this example are the same as those used in Example 5. The first amino acid residue is coupled to the resin manually on a shaker. 2.5 mmol of Fmoc-Asp(O-tBu)-OH is dissolved in 4 mL of 0.5N HBTU in
DMF. To the solution is added 1 mL of DIEA. The mixture is shaken for about 2 min. To the solution is then added 0.2 mmol of MBHA (substitution = 0.91 mmol/g) resin. The mixture is shaken for about 1 hr. The resin is washed with DMF and treated with 100% TFA for 2x15 min to remove the t-Bu protecting group. The resin is washed with DMF and is treated with HBTU (0.6 mmol) and DIEA (1mL) in 4 mL of DMF for about 15 min. 0.6 mmol of 1-tetradecaneamine is added to the reaction mixture and the mixture is shaken for about 1 hr. The resin is washed with DMF and treated with 25% piperidine in DMF for 2x20 min to remove the Fmoc protecting group. The resin is washed with DMF and transferred to the reaction vessel of the peptide synthesizer to continue the synthesis. The remaining synthesis and purification procedures for the peptide of this example are the same as those described for the synthesis of Example 1.
The syntheses of other compounds of the present invention containing
Asp(1-alkylamino) or Glu(1-alkylamino) residue are carried out in an analogous manner as described for the synthesis of Example 12. Fmoc-Asp(O-tBu)-OH or
Fmoc-Glu(O-tBu)-OH amino acid is used for the residue of Asp(1-alkylamino) or
Glu(1-alkylamino), respectively, in the peptide, while Boc-Asp(OcHex)-OH or
BocGlu(OcHex)-OH amino acid is used for the residue of Asp or Glu, respectively.
the Asp(1-alkylamino) or Glu(1-alkylamino) residue is not at the C-terminus, the peptide fragment immediately prior to the Asp(1-alkylamino) or Glu(1alkylamino) residue is assembled on the resin on the peptide synthesizer first.
Example 13 (Aib8.35, Arg26'34, Lys38(Ne-tetradecanoyl),13-Ala 37)hGLP-1(7-37)-OH
The Boc amino acids used are the same as those in the synthesis of (Aib8'35, Arg26,3a Lys36(Ne-tetradecanoyl))hGLP-1(7-36)NH2 (Example 5). 270 mg
Boc-13-Ala-PAM resin (Novabiochem, San Diego, California, substitution=0.74 mmol/g) was used. The Boc protecting group on Boc-13-Ala-PAM resin was deblocked on a shaker with 100%TFA for 2x2 min first. The remainder of the synthesis and purification procedures were the same as that in Example 5. 83.0 mg of the title peptide was obtained as white solid. Purity was 99% based on analytical HPLC analysis. Electro-spray mass spectrometer analysis gave the molecular weight at 3650.5 in agreement with the calculated weight 3650.8.
Example 14 (Aib8'35, Arg26.34, Lys36(Ne-tetradecanoyl))hGLP-1(7-36)-OH
The Boc amino acids to be used are the same as those in the synthesis of (Aib8,35, Arg26,34, Lys36(NE-tetradecanoyl))hGLP-1(7-36)NH2 (Example 5). FmocLys(Boc)-OH (2.5 mmol) is pre-activated with HBTU (2.0 mmol), HOBt (2.0 mmol and DIEA (2.5 ml) in DMF (4 ml) for about 2 min. This amino acid is coupled to
mg of PAM resin (Chem-Impex, Wood Dale, IL; substitution = 0.85 mmol/g) manually on a shaker. The coupling time is about 8 hrs. The remainder of the synthesis and purification procedures are the same as those in Example 5.
Electro-spray mass spectrometer analysis gave the molecular weight at 3579.15
agreement with the calculated weight 3579.5.
The syntheses of other analogs of hGLP-1(7-36)-OH, hGLP-1(7-37)-OH and hGLP-1(7-38)-OH of the instant invention which contain Lys(NE-alkanoyl) residue can be carried out in an analogous manner according to the procedure described for the synthesis of Example 14. Fmoc-Lys(Boc)-OH amino acid is used for the residue of Lys(NE-alkanoyl) in the peptide, while Boc-Lys(2CIZ)-OH amino acid is used for the residue of Lys.
Example 366 (AibB, 13-Ala35, Aec37)hGLP-1(7-37)NH2
A mixture of MBHA resin (0.2mmol, substitution=0.91 mmol/g), Fmoc-Aec OH (0.40g, 0.829 mmol), HBTU (1.5 mL @ 0.5M in DMF) and DIEA (0.5mL) in a reaction vessel was shaken on a shaker for 4h at room temperature. The resin was then washed with DMF and treated with 25% piperidine in DMF for 2X20min. The resin was washed with DMF and DCM and transferred to the reaction vessel of the peptide synthesizer to continue the assembly of the rest of the peptide according the procedure described for Example 1. The purification procedure was also the same as the one described in Example 1. Electro-spry mass spectrometer analysis gave the molecular weight at 3494.8 in agreement with the calculated molecular weight 3494.99. Purity 93%; Yield 79.1 mg.
Example 367 (AibB, 13-Ala35, Aec38)hGLP-1(7-38)NH2
Example 367 was synthesized substantially according to the procedure described for Example 366. MS(ES)=3551.7, calculated MW=3552.04; Purity 97%;
Yield 97.4mg.
Example 368: (AibB, 13-Ala35, Aec37 38)hGLP-1(7-38)NH2
A mixture of MBHA resin (0.2mmol, substitution=0.91 mmol/g), Fmoc-AecOH (0.289g, 0.6 mmol), HBTU (1.12 mL @ 0.5M in DMF) and DIEA (0.4mL) in a reaction vessel was shaken on a shaker for 2h at room temperature. The resin was then washed with DMF and treated with 30% piperidine in DMF for 2X15min. The resin was washed with DMF. To the reaction vessel were added Fmoc-Aec-OH (0.289g, 0.6 mmol), HBTU (1.12 mL @ 0.5M in DMF) and DIEA (0.4mL). The mixture was shaken at room temperature for 2h. The resin was washed with DMF and treated with 30% piperidine in DMF for 2X15min. The resin was washed with
DMF and DCM and transferred to the reaction vessel of the peptide synthesizer
continue the assembly of the rest of the peptide according the procedure described for Example 1. The purification procedure was also the same as the one described in Example 1. Electro-spry mass spectrometer analysis gave the molecular weight at 3663.9 in agreement with the calculated molecular weight 3664.26. Purity
Yield 75.3mg.
Example 369 (Aib8, Arg26.34, 13-Ala 35, Lys36(N-Aec-decanoyl))hGLP-1(7-36)NH2
A mixture of MBHA resin (0.2mmol, substitution=0.91 mmol/g), BocLys(Fmoc)-OH (1.17g, 2.5mmol), HBTU (4 mL @ 0.5M in DMF) and DIEA (1 mL) in a reaction vessel was shaken on a shaker at room temperature for 10min. The resin was washed with DMF and treated with 25% piperidine in DMF for 2X15min.
The resin was washed with DMF. To the reaction vessel were added Fmoc-Aec-OH (0.289g, 0.6 mmol), HBTU (1.12 mL @ 0.5M in DMF) and DIEA (0.4mL). The mixture was shaken at room temperature for 10min. The resin was washed with
DMF and treated with 30% piperidine in DMF for 2X15min. The resin was washed with DMF and treated with a mixture of decanoic acid (431 mg, 2.5 mmol), HBTU
mL @ 0.5M in DMF) and DIEA (1mL) for 10 min. The resin was washed with DMF and treated with 100% TFA for 2X2 min. The resin was washed with DMF and
DCM and transferred to the reaction vessel of the peptide synthesizer to continue the assembly of the rest of the peptide according the procedure described for
Example 1. The purification procedure was also the same as the one described
Example 1. Electro-spry mass spectrometer analysis gave the molecular weight
3677.0 in agreement with the calculated molecular weight 3677.25. Purity 97.6%;Yield 44.8mg.
The following examples can be made according to the appropriate procedures described hereinabove.
Example 15: (Aib35)hGLP-1(7-36)NH2
Example 16: (/3-Ala 35)hGLP-1(7-36)NH2
Example 17: ((N"-Me-His)7, Aib8.35)hGLP-1(7-36)NH2
Example 18: ((N"-Me-HIS)', Aib8, (3-Ala35)hGLP-1(7-36)NH2
Example 19: ((N"-Me-His)', Aib8-35 Arg26.34)hGLP-1(7-36)NH2
Example 20: ((Na-Me-His)7, Aib8, Arg26,34, 13-A1a35)hGLP-1(7-36)NH2
Example 21: (Aib8, A6C35)hGLP-1(7-36)NH2
Example 22: (Aib8, A5c35)hGLP-1(7-36)NH2
Example 23: (Aib8, D-A1a35)hGLP-1(7-36)NH2
Example 24: (Aib8,35, A6c32)hGLP-1(7-36)NH2
Example 25: (Aib1,35, A5c32)hGLP-1(7-36)NH2
Example 26: (Aibe'35, GIU23)hGLP-1(7-36)NH2
Example 27: (Aibe'24.35)hGLP-1(7-36)NH2
Example 28: (AibB30,35)hGLP-1(7-36)NH2
Example 29: (Aib8,25,35)hGLP-1(7-36)NH2
Example 30: (Aiba,35, A6c16'20)hGLP-1 (7-36)NH2
Example 31: (Aib8'35, A6c 16,29.32 )hGLP-1 (7-36)NH2
Example 32: (Aib8'35, A6c20'32)hGLP-1(7-36)NH2
Example 33: (Aib8'35, A6c20)hGLP-1(7-36)NH2
Example 34: (Aib8'35, Lys25)hGLP-1(7-36)NH2
Example 35: (Aib8'24,35, A6c20)hGLP-1(7-36)NH2
Example 36: (Aib8.35, A6c29,32)hGLP-1(7-36)NH2
Example 37: (Aib8'24,35, A6C29,32)hGLP-1(7-36)NH2
Example 38: (Aib8'35, A6c12)hGLP-1(7-36)NH2
Example 39: (Aib8,35, Cha20)hGLP-1(7-36)NH2
Example 40: (Aib1,35, A6c33)hGLP-1(7-36)NH2
Example 41: (Aib8'35, A6c20,32)hGLP-1(7-36)NH2
Example 42: (Aib8, A6c16'20, I3-Ala35)hGLP-1(7-36)NH2
Example 43: (Aib8,35, 13_Ala22)hGLP-1(7-36)NH2
Example 44: (Aib8 22,35)hGLP-1(7-36)NH2
Example/ 45: (Aib1.35, GIu23, A6c32)hGLP-1(7-36)NH2
Example 46: (Aib8,24,35, GIU23, A6C32)hGLP-1(7-36)NH2
Example 47: (Aib8.24,25,35, GIu23, A6c32)hGLP-1(7-36)NH2
Example 48: (Aib8,24,25,35, A6c16,20,32, GIU23)hGLP-1(7-36)NH2
Example 49: (Aib8, A6c32, 13-Ala35)hGLP-1(7-36)NH2
Example 50: (Aib8, A5c32, l3-Ala35)hGLP-1(7-36)NH2
Example/ 51: (Aib8, GIu23, 13-Ala 35)hGLP-1(7-36)NH2
Example 52: (Aib6'24, (3-Ala 35)hGLP-1(7-36)NH2
Example 53: (Aib8,30 13-Ala 35)hGLP-1(7-36)NH2
Example 54: (Aib8'25, 13-Ala 35)hGLP-1(7-36)NH2
Example 55: (Aib8, A6c16'20, I3-Ala35)hGLP-1(7-36)NH2
Example 56: (Aib8, A6c'6.29,32 13-Ala 35)hGLP-1(7-36)NH2
Example 57: (AibB, A6c20.32, /3_A1a35)hGLP-1(7-36)NH2
Example 58: (AibB, A6c20, 13-Ala 35)hGLP-1(7-36)NH2
Example 59: (AibB, Lys25, 13-Ala 35)hGLP-1(7-36)NH2
Example 60: (Aib1.21, A6c20,13-A1a35)hGLP-1(7-36)NH2
Example 61: (Aib8, A6c29.32, t3_AIa35)hGLP-1 (7-36)NH2
Example 62: (AIbB 24, A6C29,32, 13_Ala35)hGLP-1(7-36)NH2
Example 63: (AibB, A6c12, 13-A1a35)hGLP-1(7-36)NH2
Example 64: (AibB, Cha20, 13-Ala 35)hGLP-1(7-36)NH2
Example 65: (Ai b' A6C33, 13-Ala 35)hGLP-1(7-36)NH2
Example 66: (Aib8, A6C20,32, 13_Ala35)hGLP-1(7-36)NH2
Example 67: (Aib8, 13-Ala 22,35)hGLP-1(7-36)NH2
Example 68: (AIbB.22, 13-Ala 35)hGLP-1(7-36)NH2
Example 69: (Aib8, GIu23, A6c32, 13-Ala35)hGLP-1(7-36)NH2
Example 70: (Aib8.24 GIu23, A6c32, 13-Ala 35)hGLP-1(7-36)NH2
Example 71: (Aib8'24, GIu23, A6c32, Lys34(NE-octanoyl), 13-Ala 35)hGLP-1(7Example 72: (Aib824.25, GIU23, A6C32, 13-Ala35)hGLP-1(7-36)NH2
Example 73: (Aib8,24.25, A6c'6,20.32, GIU23, /3-Ala 35)hGLP-1(7-36)NH2
Example 74: (AIb8.35, D-Arg36)hGLP-1(7-36)NH2
Example 75: (Aib8'3S, D-Lys36)hGLP-1(7-36)NH2
Example 76: (Aib8, 13-Ala35, D-Arg36)hGLP-1(7-36)NH2
Example 77: (AIbB, 13-Ala35, D-Lys36)hGLP-1(7-36)NH2
Example 78; (Aib8=35, Arg28'34)hGLP-1(7-36)NH2
Example 79: (Aib8, Arg26,34, 13-Ala 35)hGLP-1(7-36)NH2
Example 80: (Aib8'35, Arg25,26.34)hGLP-1(7-36)NH2
Example 81: (Aib8, Arg25,26,34 13-Ala 35)hGLP-1(7-36)NH2
Example 82: (Aib8, Arg26,34, /3_Ala35, Lys38(N`-tetradecanoyl))hGLP-1(7-36)OH
Example 83: (Aib835, Arg26,3a Lys36(N'-tetradecanoyl))hGLP-1(7-37)OH
Example 84: (Aib8,35,37, Arg26,34, Lys36(N`-tetradecanoyl))hGLP-1(7-37)OH
Example 85: (AIb8,35, Arg26,34, Lys38(N`-tetradecanoyl), D-Ala 37)hGLP-1(7Example 86: (Aiba,35.31, Arg26,34, Lys36(N`-tetradecanoyl))hGLP-1(7-38)OH
Example 87: (Aib8'3S, Arg26,34, f3-Ala 37, Lys38(NE-tetradecanoyl))hGLP-1(7Example 88: (Aib8,35, Arg26.34, Lys38(NE-tetradecanoyl))hGLP-1(7-38)OH
Example 89: (AIb8, Arg26'34, Lys36(NE-tetradecanoyl), 13-Ala 37)hGLP-1(7-37)OH
Example 90: (Aib8'37, Arg26'34, Lys38(NE-tetradecanoyl))hGLP-1(7-37)OH
Example 91: (Aib835, Arg26.3a, Ado37)hGLP-1(7-37)OH
Example 92: (Aib8,35, Arg26,34, Ado31)hGLP-1(7-37)NH2
Example 93: (Aib8, Arg26'34, Lys36(N`-tetradecanoyl), D-Ala 37)hGLP-1(7-37)OH
Example 94: (Aib8'31, Arg26,34, Lys38(NE-tetradecanoyl))hGLP-1(7-38)OH
Example 95: (Aib8, Arg26'34, 13-Ala 37, Lys38(NE-tetradecanoyl))hGLP-1(7-38)OH
Example 96: (Aib8,35, Lys26(NE-octanoyl))hGLP-1(7-36)NH2
Example 97: (AIb8,35 , Lys26(NE-tetradecanoyl))hGLP-1(7-36)NH2
Example 98: (Aib8'35, Lys26(N-hexadecanoyl))hGLP-1(7-36)NH2
Example 99: (AibB, Lys26(N-octanoyl), 13-A1a35)hGLP-1(7-36)NH2
Example 100: (Aib8, Lys26(NE-tetradecanoyl), 13-Ala 35)hGLP-1(7-36)NH2
Example 101: (Aib8, Lys28(NE-hexadecanoyl), 13-A1a35)hGLP-1(7-36)NH2
Example 102: (Aibe,35, Lys26(NE-octanoyl), Arg34)hGLP-1(7-36)NH2
Example 103: (Aib8.35, Lys26(NE-tetradecanoyl), Arg')hGLP-1(7-36)NH2
Example 104: (AIb835, Lys26(NE-hexadecanoyl), Arg34)hGLP-1(7-36)NH2
Example 105: (Aib8'35, Lys26(NE-decanoyl), Arg34)hGLP-1(7-36)NH2
Example 106: (Aib8.35, Lys25, Lys26(NE-octanoyl), Arg34)hGLP-1(7-36)NH2
Example 107: (Aib8.35, Lys25, Lys26(N-tetradecanoyl), Arg34)hGLP-1(7-36)NH2
Example 108: (Aib8,35, Lys25, Lys26(N-hexadecanoyl), Arg34)hGLP-1(7-36)NH2
Example 109: (Aib8 31, Arg25,34, Lys28(NE--octanoyl))hGLP-1(7-36)NH2
Example 110: (Aib8,35, Arg25'34, Lys26(NE-tetradecanoyl))hGLP-1(7-36)NH2
Example 111: (AIb8,35, Arg25,34, Lys26(NE-hexadecanoyl))hGLP-1 (7-36)NH2
Example 112: (Aib8'35, Arg25.3', Lys26(NE_decanoyl))hGLP-1(7-36)NH2
Example 113: (Aib8, Lys26(NE-octanoyl), Arg34, 13-Ala 35)hGLP-1(7-36)NH2
Example 114: (Aib8, Lys26(NE-tetradecanoyl), Arg, 13-Ala 35)hGLP-1(7-36)NH2
Example 115: (Aib8, Lys28(NE-hexadecanoyl), Arg34, 13-Ala 35)hGLP-1(7-36)NH2
Example 116: (Aib8, Lys26(N-decanoyl), Arg34, 13-Ala 31)hGLP-1(7-36)NH2
Example 117: (Aibe,35 Lys'(NE-octanoyl))hGLP-1(7-36)NH2
Example 118: (Aib835, Lys34(NE-tetradecanoyl))hGLP-1(7-36)NH2
Example 119: (Aib8 35, Lys34(NE-hexadecanoyl))hGLP-1(7-36)NH2
Example 120: (Aib8,35, Arg26, Lys34(Ne-octanoyl))hGLP-1(7-36)NH2
Example 121: (Alb8'35, Arg26, Lys34(Ne-hexadecanoyl))hGLP-1(7-36)NH2
Example 122: (Aib8'35, Arg26, Lys34(N-decanoyl))hGLP-1(7-36)NH2
Example 123: (Aib8,31, Arg25.26, Lys34(NE-octanoyl))hGLP-1(7-36)NH2
Example 124: (Aibe.35, Arg25.26, Lys34(NE-tetradecanoyl))hGLP-1(7-36)NH2
Example 125: (Alba 35, Arg25'26, Lys34(NE-hexadecanoyl))hGLP-1(7-36)NH2
Example 126: (Aib8'35, Arg25'26, Lys34(N`-decanoyl))hGLP-1(7-36)NH2
Example 127: (Aib8 35, Lys25, Arg26, Lys34(NE-octanoyl))hGLP-1(7-36)NH2
Example 128: (Aib835, Lys25, Arg26, Lys34(NE-tetradecanoyl))hGLP-1(7-36)NH2
Example 129: (Aib8'35, Lys25, Arg26, Lys34(NE-hexadecanoyl))hGLP-1(7-36)NH2
Example 130: (Aib8 35, Lys36(NE-octanoyl))hGLP-1(7-36)NH2
Example 131: (Aibe35, Lys38(NE-tetradecanoyl))hGLP-1(7-36)NH2
Example 132: (Aib8'35, Lys36(NE-hexadecanoyl))hGLP-1(7-36)NH2
Example 133: (Aib8,35, Arg26, Lys36 (NE-octanoyl))hGLP-1(7-36)NH2
Example 134: (Aib8,35, Arg26, Lys36(Ne-tetradecanoyl))hGLP-1(7-36)NH2
Example 135: (Aib8'35, Arg26, Lys36(NE-hexadecanoyl))hGLP-1(7-36)NH2
Example 136: (Aib8,35, Arg26,34, Lys38(NE-octanoyl))hGLP-1(7-36)NH2
Example 137: (Aib8.35, Arg26,34, Lys36(NE-hexadecanoyl))hGLP-1(7-36)NH2
Example 138: (AIb6,35, Arg26,34, Lys38(NE-octanoyl))hGLP-1(7-38)NH2
Example 139: (Alba 35, Arg26'34, LyS38(NE-decanoyl))hGLP-1(7-38)NH2
Example 140: (Aib8,35, Arg26,34, Lys38(Ne-tetradecanoyl))hGLP-1(7-38)NH2
Example 141: (AIb6,35, Arg26,34, Lys38(NE-hexadecanoyl))hGLP-1(7-38)NH2
Example 142: (Aibs.35.37, Arg25,28,34, LyS38(NE-octanoyl))hGLP-1(7-38)NH2
Example 143: (AIb6,35,37, Arg25,26.34, LyS38(NE-decanoyl))hGLP-1(7-38)NH2
Example 144: (Aibe35,37, Arg25,26,34, Lys38(NE-tetradecanoyl))hGLP-1(7-38)NH2
Example 145: (Aib835,37, Arg25.26.34, Lys38(NE-hexadecanoyl))hGLP-1(7-38)NH2
Example 146: (AIb835,37, Arg26,34, Lys38(Ne-octanoyl))hGLP-1(7-38)NH2
Example 147: (Aib835,37, Arg26,34, Lys38(NE-decanoyl))hGLP-1(7-38)NH2
Example 148: (Aiba,35,37, Arg26.34, Lys38(NE-hexadecanoyl))hGLP-1(7-38)NH2
Example 149: (Aib8,35,37, Arg25,26,34, Lys38(Ne-oetanoyl))hGLP-1(7-38)NH2
Example 150: (AIb8,35,37, Arg25,26.34, Lys38(NE-decanoyl))hGLP-1(7-38)NH2
Example 151: (Aib6.35.37, Arg25.26.34, LyS38(NE-tetradecanoyl))hGLP-1(7-38)NH2
Example 152: (Aib8.35,37, Arg25,26,34, Lys38(NE-hexadecanoyl))hGLP-1(7-38)NH2
Example 153: (Aib835, Lys25, Arg26.34, Lys36(NE-octanoyl))hGLP-1(7-36)NH2
Example 154: (Aib8'35, Lys25, Arg2834, Lys36(NE-tetradecanoyl))hGLP-1(7-36)NH2
Example 155: (Aib8.35, Lys25, Arg26'34, Lys36(NE-hexadecanoyl))hGLP-1(7-36)NH2
Example 156: (Aib8.35, Arg25,26.34, Lys38(NE-octanoyl))hGLP-1(7-36)NH2
Example 157: (Aib8.31, Arg25,26.34, Lys'(NE-tetradecanoyl))hGLP-1(7-36)NH2
Example 156: (Aib8,35, Arg25,26,34, Lys36(NE-hexadecanoyl))hGLP-1(7-36)NH2
Example 159: (AIbB'35, Arg25'26,3a Lys36(NE-decanoyl))hGLP-1(7-36)NH2
Example 160: (Aib8, Lys34(NE-octanoyl), 13-A1a35)hGLP-1(7-36)NH2
Example 161: (Aib8, Lys'(NE-tetradecanoyl), 13-Ala 35)hGLP-1(7-36)NH2
Example 162: (Aib8, Lys34(NE-hexadecanoyl), 13-Ala 35)hGLP-1(7-36)NH2
Example 163: (Aib8, A6c32, Lys34(NE-octanoyl), 13-Ala35)hGLP-1(7-36)NH2
Example 164: (Aib8, GIu23, Lys34(NE-octanoyl), 13-Ala 35)hGLP-1(7-36)NH2
Example 165: (Aib8, GIu23, A6c32, Lys'(NE-octanoyl), 13-Ala 35)hGLP-1(7-36)NH2
Example 166: (Aib8, Arg28, Lys3(NE-octanoyl), 13-Ala )hGLP-1(7-36)NH2
Example 167: (Aib8, Arg26 , Lys34(NE-tetradecanoyl), 13-Ala 35)hGLP-1(7-36)NH2
Example 168: (Aib8, Arg26, Lys34(NE-hexadecanoyl), /3-Ala 31)hGLP-1(7-36)NH2
Example 169: (Aib8, Arg28, Lys34(NE-decanoyl), 13-Ala 35)hGLP-1(7-36)NH2
Example 170: (Aib8, Arg25,26, Lys4(NE-octanoyl), 13-A1a35)hGLP-1(7-36)NH2
Example 171: (Aib8, Arg25,26, Lys34(NE-tetradecanoyl), 13-Ala 35)hGLP-1(7Example 172: (Aib8, Arg25'26, Lys34(NE-hexadecanoyl), (3-Ala 35)hGLP-1(7Example 173: (Aib8, Arg25,26, Lys34(NE-decanoyl), 13-Ala 35)hGLP-1(7-36)NH2
Example 174: (Aib8, Lys25, Arg26, Lys34(NE-octanoyl), 13-A1a35)hGLP-1(7-36)NH2
Example 175: (Aib8, Lys25, Arg26, Lys34(NE-tetradecanoyl), 13-Ala 35)hGLP-1(7Example 176: (Aib8, Lys25, Arg26, Lys34(NE-hexadecanoyl), 13-Ala35)hGLP-1(7Example 177: (Aib8, 13-Ala 35, Lys38(NE-octanoyl))hGLP-1(7-36)NH2
Example 178: (Aib8, /3-Ala35, Lys36(N-tetradecanoyl))hGLP-1(7-36)NH2
Example 179: (Aib8, 13-Ala35, Lys36(N-hexadecanoyl))hGLP-1(7-36)NH2
Example 180: (Aib8, Arg26, /3-Ala35, LyseG(NE-octanoyl))hGLP-1(7-36)NH2
Example 181: (Aib8, Arg26, 13-Ala35, Lys36(NE-tetradecanoyl))hGLP-1(7-36)NH2
Example 182: (Aib8, Arg26, 13-Ala35, Lys36(NE-hexadecanoyl))hGLP-1(7-36)NH2
Example 183: (Aib8, Arg26,34, f3-Ala 35, Lys36(NE-octanoyl))hGLP-1(7-36)NH2
Example/ 184: (Aib8, Arg26,34 /3-Ala 35, Lys36(N`-tetradecanoyl))hGLP-1(7Example 185: (Aib8, Arg26,3a 13-Ala35, Lys36(N`- hexadecanoyl))hGLP-1(7-36)NH2
Example 186: (Aib8, Arg28=34, /3-Ala35, Lys36(N`-decanoyl))hGLP-1(7-36)NH2
Example 187: (Aib8, Lys25, Arg26'34, 8-AIa35, Lys36(N`-octanoyl))hGLP-1(7Example 188: (Aib8, Lys25, Arg28'34, Lys36(Ne-tetradecanoyl), 13-A1a35)hGLP-
Example 189: (Aib8, Lys25, Arg26,34 13-AIa35, Lys36(N`-hexadecanoyl))hGLP-1(7Example 190: (Aib8, Arg25,26,34, 13_Ala35, Lys36(N`-octanoyl))hGLP-1(7-36)NH2
Example 191: (Aib8, Arg25,26,34 13-Ala 35, Lys36(N`-tetradecanoyl))hGLP-1(7Example 192: (Aib8, Arg25,26,34, 13_AIa35, Lys36(N`-hexadecanoyl))hGLP-1(7Example 193: (Aib8, Arg25,26,34, /3_AIa35, Lys36(N`-decanoyl))hGLP-1(7-36)NH2
Example 194: (Aibe,35, Lys26(N`-octanoyl), A6c32, Arg34)hGLP-1(7-36)NH2
Example 195: (Aib8.35, Lys26(N`-tetradecanoyl), A6c32, Arg34)hGLP-1(7-36)NH2
Example 196: (Aib8,35, Lys28(N`-hexadecanoyl), A6c32, Arg34)hGLP-1(7-36)NH2
Example 197: (Aib835, A6c32, Lys34(N`-octanoyl))hGLP-1(7-36)NH2
Example 198: (Aib8,31, A6c32, Lys34(N-tetradecanoyl))hGLP-1(7-36)NH2
Example 199: (Aib8.35, A6c32, Lys34(N hexadecanoyl))hGLP-1(7-36)NH2
Example 200: (Aib8,31, Arg26, A6c32, Lys34(NE-octanoyl))hGLP-1(7-36)NH2
Example 201: (Aib8,35, Arg26, A6c32, Lys34 (NE-tetradecanoyl))hGLP-1(7-36)NH2
Example 202: (Aib8=35, A6c32, Lys36(N`-octanoyl))hGLP-1(7-36)NH2
Example 203: (Aib8,35, A6c32, Lys36(N`-tetradecanoyl))hGLP-1(7-36)NH2
Example 204: (Aib835, A6c32, Lys36(NE-hexadecanoyl))hGLP-1(7-36)NH2
Example 205: (Aib8'35, Arg26, A6c32, Lys36(Nε-octanoyl))hGLP-1 (7-36)NH2
Example 206: (Aib6.35, Arg26, A6c32, Lys38(N`-tetradecanoyl))hGLP-1 (7-36)NH2
Example 207: (Aib8=35, Arg26, A6c32, Lys36(N`-hexadecanoyl))hGLP-1(7-36)NH2
Example 208: (Aib8'35, Arg26.34, A6c32, Lys36(N`-octanoyl))hGLP-1(7-36)NH2
Example 209: (Aib8,35, Arg26,34 A6c32, Lys38(Ne-decanoyl))hGLP-1(7-36)NH2
Example 210: (Aib11,35, Arg26,34, A6c32, Lys36(N`-tetradecanoyl))hGLP-1(7Example 211: (Aibe'35, Arg26'34, A6c32, Lys36(N`-hexadecanoyl))hGLP-1(7-36)NH2
Example 212: (Aib8.24'35, Lys26(NE-octanoyl), Arg34)hGLP-1(7-36)NH2
Example 213: (Aib8.24,35, Lys26(NE-tetradecanoyl), Arg34)hGLP-1(7-36)NH2
Example 214: (Aib8,24,35, Lys26(NE-hexadecanoyl), Arg')hGLP-1(7-36)NH2
Example 215: (Aib8,24,35, Arg26, Lys34(NE-octanoyl))hGLP-1(7-36)NH2
Example 216: (Aib8'24,35, Arg26, Lys34(N-tetradecanoyl))hGLP-1(7-36)NH2
Example 217: (Aib8.14'35, Arg26, Lys34(NE-hexadecanoyl))hGLP-1(7-36)NH2
Example 218: (AibB'24,35, Arg26,34, Lys36(NE-octanoyl))hGLP-1(7-36)NH2
Example 219: (Aib8.24,35, Arg26,34, Lys38(NE-tetradecanoyl))hGLP-1(7-36)NH2
Example 220: (Aib8 24,35 Arg26,34, Lys36(NE-hexadecanoyl))hGLP-1(7-36)NH2
Example 221: (Aib8=24.35, GIu23, A6c32, Lys34(NE-octanoyl))hGLP-1(7-36)NH2
Example 222: (Aib8,35, GIu23, Lys28(NE-octanoyl), Arg3'')hGLP-1(7-36)NH2
Example 223: (AIb8'35, GIu23, Lys26(NE-tetradecanoyl), Arg34)hGLP-1(7-36)NH2 lo Example 224: (Aib8.35, GIu23, Lys26(NE-hexadecanoyl), Arg34)hGLP-1(7-36)NH2
Example 225: (Aib835, GIu23, Lys34(NE-octanoyl))hGLP-1(7-36)NH2
Example 226: (Aib8,35, GIu23, A6c32, Lys34(NE-octanoyl))hGLP-1(7-36)NH2
Example 227: (Aib8'35, GIu23, Arg26, Lys34(NE-octanoyl))hGLP-1(7-36)NH2
Example 228: (Aib8,35, GIu23, Arg28, Lys3''(NE-tetradecanoyl))hGLP-1(7-36)NH2
Example 229: (Aib8.35, GIu23, Arg26, Lys34(NE-hexadecanoyl))hGLP-1(7-36)NH2
Example 230: (Aib8'35, GIu23, Lys36(NE-octanoyl))hGLP-1(7-36)NH2
Example 231: (Aib8.35, GIu23, Lys36(NE-tetradecanoyl))hGLP-1(7-36)NH2
Example 232: (AIb8=35, GIu23, Lys38(NE-hexadecanoyl))hGLP-1(7-36)NH2
Example 233: (Aib35, GIu23, Arg26'34, Lys38(NE-octanoyl))hGLP-1(7-36)NH2
Example 234: (AIb8,35, GIu23, Arg26,34, Lys36(NE-tetradecanoyl))hGLP-1(7Example 235: (Aibe=35, G1u23, Arg26,34, Lys36(NE-hexadecanoyl))hGLP-1(7-36)NH2
Example 236: (Aibe30,35, Lys28(NE-octanoyl), Arg34 )hGLP-1 (7-36)NH2
Example 237: (Aib8,30.35, Lys26(NE-tetradecanoyl), Arg34)hGLP-1(7-36)NH2
Example 238: (Aib'30'35, Lys28(NE-hexadecanoyl), Arg34)hGLP-1(7-36)NH2
Example 239: (Aib8,3035, Arg26, Lys3'(NE-octanoyl))hGLP-1(7-36)NH2
Example 240: (Aib8'30=35, Arg26, Lys34(NE-tetradecanoyl))hGLP-1(7-36)NH2
Example 241: (Aib8,30,35, Arg26, Lys34(NE-hexadecanoyl))hGLP-1(7-36)NH2
Example 242: (Aib8.30,35, Arg28'`, Lys36(NE-octanoyl))hGLP-1(7-36)NH2
Example 243: (Aib8,30,35, Arg26,3a Lys36(NE-tetradecanoyl))hGLP-1(7-36)NH2
Example 244: (Aib8 30,35, Arg26.34, Lys36(NE-hexadecanoyl))hGLP-1(7-36)NH2
Example 245: (Aib8=35, GI U13, A6c32, Lys36(NE-octanoyl))hGLP-1(7-36)NH2
Example 246: (Aib835, GIu23, A6c32, Lys36(NE-tetradecanoyl))hGLP-1(7-36)NH2
Example 247: (Aib6 35, GIu23, A6c32, Lys36(N`-hexadecanoyl))hGLP-1(7-36)NH2
Example 248: (Aib6'31, GIu23, Arg26,34, A6c32, Lys36(N`-octanoyl))hGLP-1(7Example 249: (Aib8 35, GIu23, Arg28,34, A6c32, Lys38(NE-tetradecanoyl))hGLP-
Example 250: (Aib8'35, GIu23, Arg28'34, A6c32, Lys36(N`-hexadecanoyl))hGLP-1(7Example 251: (Aib624,35, GIu23, Arg26'34, A6c32, Lys36(N`-octanoyl))hGLP-1(7Example 252: (Aib8.24,35, GI U23, Arg26.34, A6c32, Lys38(N`tetradecanoyl))hGLP-1(7-36)NH2
Example 253: (Aib8'24,35, GIu23, Arg26,34, A6c32, Lys38(N`-hexadecanoyl))hGLP-
Example 254: (Aib8.24,30,35 G1u23, Arg26,34, A6c32, Lys36(N`-octanoyl))hGLP-
Example 255: (Aib8'2430.35, GIu23, Arg26.34, A6c32, Lys36(N`tetradecanoyl))hGLP-1(7-36)NH2
Example 256: (Aib6,24,30,35, GIu23, Arg26,34, A6c32, Lys3G(N`hexadecanoyl))hGLP-1(7-
Example 257: ((N'-HEPES-HiS)7, Aib35)hGLP-1(7-36)NH2
Example 258: ((Na-HEPES-His)7, 13-A1a35)hGLP-1(7-36)NH2
Example 259: ((Na-HEPES-HIS)7, Aib6, 13-Ala 35)hGLP-1(7-36)NH2
Example 260: ((Na-HEPA-His)7, Aib35)hGLP-1(7-36)NH2
Example 281: ((Na-HEPA-HiS)7, 13-Ala 35)hGLP-1(7-36)NH2
Example 262: ((N'-HEPA-HIS)7, Aib6, 13-Ala 35)hGLP-1(7-36)NH2
Example 263: ((No-tetradecanoyl-His )7, Aib35)hGLP-1(7-36)NH2
Example 264: ((Na-tetradecanoyl-His)7, 13-Ala 35)hGLP-1(7-36)NH2
Example 265: ((Na-tetradecanoyl-His)7, Aib8=35)hGLP-1(7-36)NH2
Example 266: ((Na-tetradecanoyl-His)7, AibB, /3-Ala35)hGLP-1(7-36)NH2
Example 267: ((Na-tetradecanoyl-His)7 Arg26,3a Aib35)hGLP-1(7-36)NH2
Example 268: ((Na-tetradecanoyl-His )7, Arg26'34, 13-Ala35)hGLP-1(7-36)NH2
Example 269: ((Na-tetradecanoyl-His)7, Aib8'35, Arg26'34)hGLP-1(7-36)NH2
Example 270: ((N(-tetradecanoyl-His)7, Aib6, Arg26.34, /3-Ala 35)hGLP-1(7Example 271: ((Na-tetradecanoyl-His)7, Arg25,26,34 (3-Ala 35)hGLP-1(7-36)NH2
Example 272: ((Nu-tetradecanoyl-His)?, Aib8'35 , Arg25'26'34)hGLP-1(7-36)NH2
Example 273: ((Na-tetradecanoyl-His)7, AibB, Arg25,26,34, /3-Ala 35)hGLP-1(7Example 274: (Aib8'35, Lys26(N`-octanesulfonyl), Arg34)hGLP-1(7-36)NH2
Example 275: (Aib6,35, Lys26(NE-dodecanesulfonyl), Arg34)hGLP-1(7-36)NH2
Example 276: (Aib8.35, Lys26(N`-hexadecanesulfonyl), Arg34 )hGLP-1 (7-36)NH2
Example 277: (A1b8 35, Arg26, Lys34(N`-octanesulfonyl))hGLP-1(7-36)NH2
Example 278: (Aib6'35, Arg26, Lys34(NE-dodecanesulfonyl))hGLP-1(7-36)NH2
Example 279: (Aib8-35 Arg26, Lys34(N6-hexadecanesulfonyl))hGLP-1(7-36)NH2
Example 280: (Aib8'35, Arg26,34, Lys38(N-octanesulfonyl))hGLP-1(7-36)NH2
Example 281: (Aib8.35, Arg26,34, Lys36(N`-hexadecanesulfonyl))hGLP-1(7-36)NH2
Example 282: (Aib6.35, Asp26(1-(4-decylpiperazine)), Arg34)hGLP-1(7-36)NH2
Example 283: (Aib6,35, Asp28(1-(4-dodecylpiperazine)), Arg34)hGLP-1(7-36)NH2
Example 284: (Aib8'35, Asp26(1-(4-tetradecylpiperazine)), Arg3'`)hGLP-1(7Example 285: (Aib8,35, Asp26(1-(4-hexadecylpiperazine)), Arg34)hGLP-1(7-36)NH2
Example 286: (Aibe,35, Arg26, Asp34(1-(4-decylpiperazine)))hGLP-1(7-36)NH2
Example 287: (Aib1,31, Arg26, Asp34(1-(4-dodecylpiperazine)))hGLP-1(7-36)NH2
Example 288: (Aib1,31, Arg26, Asp34(1-(4-tetradecylpiperazine)))hGLP-1(7Example 289: (Aib1,35, Arg26, Asp34(1-(4-hexadecylpiperazine)))hGLP-1(7-36)NH2
Example 290: (Aib8,35, Arg26,34, Asp3B(1-(4-decylpiperazine)))hGLP-1(7-36)NH2
Example 291: (Aib8.35, Arg26,34, Asp36(1-(4-dodecylpiperazine)))hGLP-1(7Example 292: (Aib8,35, Arg26,34, Asp38(1-(4-hexadecylpiperazine)))hGLP-1(7Example 293: (Aib8'35, Arg26.34, Asp38(1-(4-decylpiperazine)))hGLP-1(7-38)NH2
Example 294: (Aib8,35, Arg26'34, Asp38(1-(4-dodecylpiperazine)))hGLP-1(7Example 295: (Aib8 35, Arg26,34, Asp38(1-(4-tetradecylpiperazine)))hGLP-1(7Example 296: (Aib6'35, Arg26,34, Asp38(1-(4-hexadecylpiperazine)))hGLP-1(7Example 297: (Aib8,35,37, Arg26,34, Asp38(1-(4-decylpiperazine)))hGLP-1(7Example 298: (Aib835,37, Arg26,34, Asp38(1-(4-dodecylpiperazine)))hGLP-1(7Example 299: (Aib835.31, Arg26,34, Asp3B(1-(4-tetradecylpiperazine)))hGLP-1(7Example 300: (Aib8,35,37 Arg26,3a Asp38(1-(4-hexadecylpiperazine)))hGLP-1(7Example 301: (Aib8'35, Arg25.34, Asp26(1 -(4-decylpiperazine)))hGLP-1 (7Example 302: (Aib8,35, Arg25,34, Asp26(1-(4-dodecylpiperazine)))hGLP-1(7Example 303: (Aib1,35 Arg25.34 Asp26(1-(4-tetradecylpiperazine)))hGLP-1(7Example 304: (Aib8,35, Arg25,34, Asp26(1-(4-hexadecylpiperazine)))hGLP-1(7Example 305: (A1b835, Arg25,26, Asp34(1-(4-decylpiperazine)))hGLP-1(7-36)NH2
Example 306: (Aib8,35, Arg25,26, Asp34(1-(4-dodecylpiperazine)))hGLP-1(7Example 307: (Aib8,35 Arg25,26Asp34(1-(4-tetradecylpiperazine)))hGLP-1(7Example 308: (Aib8 35, Arg25,26, Asp34(1-(4-hexadecylpiperazine)))hGLP-1(7Example 309: (Aib8,35, Arg25'26'34, Asp36(1-(4-decylpiperazine)))hGLP-1(7Example 310: (Aib835, Arg25,26,34, Asp36(1-(4-dodecylpiperazine)))hGLP-1(7Example 311: (Aib8'35, Arg25,26,34 Asp 36(1 -(4-tetradecylpiperazine)))hGLP-1
Example 312: (Aib8'35, Arg25,26,3a Asp36(1-(4-hexadecylpiperazine)))hGLP-1(7Example 313: (Aib8,35, Arg25,26,34, Asp38(1-(4-decylpiperazine)))hGLP-1(7Example 314: (Aib8,35, Arg25,26,34, Asp 38(1 -(4-dodecylpiperazine)))hGLP-1 (7Example 315: (Aib8,35, Arg25,26,34, Asp38(1-(4-tetradecylpiperazine)))hGLP-1(7Example 316: (Aib1,35, Arg25,26,34, Asp38(1-(4-hexadecylpiperazine)))hGLP-1(7Example 317: (Aib8,35,37, Arg25'26,34, Asp38(1-(4-decylpiperazine)))hGLP-1(7Example 318: (Aib835,37, Arg25,26,34, Asp38(1-(4-dodecylpiperazine)))hGLP-1(7Example 319: (Aib8.35,37 Arg25.26,34, Asp38(1-(4-tetradecylpiperazine)))hGLP
Example 320: (Aib8.35,37, Arg25,26,34 Asp3B(1-(4-hexadecylpiperazine)))hGLP-
Example 321: (Aib8'35, Arg26,34, GIu38(1-dodecylamino))hGLP-1(7-36)NH2
Example 322: (Aib835, Glu28(1-dodecylamino), Arg34)hGLP-1(7-36)NH2
Example 323: (Aib8.35, Arg26, GIu34(1-dodecylamino))hGLP-1(7-36)NH2
Example 324: (Aib8,35,37 Arg26'34, GIu38(1-dodecylamino))hGLP-1(7-38)NH2
Example 325: (Aib835, Arg34, Lys28(N`-(2-(4-decyl-1-piperazine)-acetyl)))hGLP-
Example 326: (Aib8.35, Arg34, Lys26(NE-(2-(4-dodecyl-1-pipe razine)acetyl)))hGLP-1(7Example 327: (Aib8.35, Arg34, Lys26(N`-(2-(4-tetradecyl-l-pipe razine)acetyl)))hGLP-
Example 328: (Aib8'35, Arg34, Lys26(N-(2-(4-hexadecyl-1-piperazine)acetyl)))hGLP-
Example 329: (Aib8.35, Arg26, Lys34(NE-(2-(4-decyl-1-piperazine)-acetyl)))hGLP-
Example 330: (Aib8 35, Arg26, Lys34(N`-(2-(4-dodecyl-l-piperazine)acetyl))hGLP-1(7Example 331: (Aib8,35, Arg26, Lys34(N`-(2-(4-tetradecyl-1-pipe razine)acetyl)))hGLP-
Example 332: (Aib8,35, Arg26, Lys34(NE-(2-(4-hexadecyl-1-piperazine)acetyl)))hGLP-
Example 333: (AIb8,35, Arg26.34, Lys36(NE-(2-(4-decyl-1-piperazine)acetyl)))hGLP-1(7Example 334: (Ai b8,35, Arg26'34, Lys38(N`-(2-(4-dodecyl-1-piperazine)acetyl)))hGLP-1(7Example 335: (Aib8'35, Arg26,34, Lys36(N6-(2-(4-hexadecyl-1-piperazine)acetyl)))h acetyl)))hGLPExample 336: (AIb8,35, Arg26.34, Lys36(NE-(2-(4-decyl-1-piperazine)acetyl)))hGLP-1(7Example 337: (Aib8,35, Arg28'34, Lys38(NE-(2-(4-dodecyl-l -piperazine)acetyl)))hGLP-1(7Example 338: (Aib835, Arg26.34, Lys38(N`-(2-(4-tetradecyl-l -piperazine)acetyl)))hGLP-1(7-38)NH2
Example 339: (Aib8,35, Arg26.34, Lys38(N--(2-(4-hexadecyl-l-piperazine)acetyl)))hGLP-1(7-38)NH2
Example 340: (Aib8,35,37, Arg26,34, Lys38(N`-(2-(4-decyl-1-piperazine)-acetyl )))hGLP-1(7Example 341: (Aiba'35,37, Arg28,34, Lys38(NE-(2-(4-dodecyl-l-piperazine)acetyl)))hGLP-1(7Example 342: (Aib8,35,31, Arg2B,34, Lys38(N`-(2-(4-tetradecyl-1-piperazine)acetyl)))hGLP-1 (7-38)NH2
Example 343: (Aib8,35,37, Arg28'34, Lys38(N`-(2-(4-hexadecyl-1-piperazine)acetyl)))hGLP-1(7-38)NH2
Example 344: (Aib835, Arg25,3a Lys28(Ne-(2-(4-decyl-1-piperazine)acetyl)))hGLP-1(7Example 345: (AIb8,35, Arg25,34, Lys26(NE-(2-(4-dodecyl-1-piperazine)acetyl)))hGLP-1(7Example 346: (Aibe.35, Arg25.34, Lys26(N`-(2-(4-tetradecyl-1-piperazine)acetyl)))hGLP-1(7-36)NH2
Example 347: Aib6.35, Arg25.34, Lys28(N`-(2-(4-hexadecyl-1-piperazine)acetyl)))hGLP-
Example 348: (Aib8,35, Arg25,26, Lys34(N`-(2-(4-decyl-1 -piperazine)acetyl)))hGLP-1(7Example 349: (Aib8,35, Arg25,26, Lys34(N`-(2-(4-dodecyl-l -piperazine)acetyl)))hGLP-1(7Example 350: (Aib8,31, Arg25,26, Lys34(Ne-(2-(4-tetradecyl-1-piperazine)acetyl)))hGLP-1(7-36)NH2
Example 351: (Aib1,35, Arg25,26, Lys34(N`-(2-(4-hexadecyl-1-piperazine)acetyl)))h -piperazine)-
Example 352: (Aib8.35, Arg25,26,3a Lys36(N`-(2-(4-decyl-1-piperazine)acetyl)))hGLP-1(7-
Example 353: (AIb8,35, Arg25,26,34 LyS38{N`-(2-(4-dodecyl-1-piperazine)acetyl)))hGLP-1(7Example 354: (Aib8'35, Arg25,26.34, Lys36(N`-(2-(4-tetradecyl-1-piperazine)acetyl)))hGLP-1(7-36)NH2
Example 355: (Aib8'35, Arg25,26,34 Lys36(N-(2-(4-hexadecyl-l-piperazine)acetyl)))hGLP-1(7-36)NH2
Example 356: (Aib8,35, Arg25,26'34, Lys36(N`-(2-(4-decyl-1-piperazine)acetyl)))hGLP-1(7-
Example 357: (Aib8,35, Arg25,26,34 , Lys38(Ne_(2-(4-dodecyl-1-piperazine)acetyl)))hGLP-1(7Example 358: (Aibe,35, Arg25,26,34, Lys38(N`-(2-(4-tetradecyl-1-piperazine)acetyl)))hGLP-1 (7-38)NH2
Example 359: (Aib8,35, Arg25,26,34 Lys38(N`-(2-(4-hexadecyl-1-piperazine)acetyl)))hGLP-1(7-38)NH2
Example 360: (Aib8,35,37 Arg25.26,34, Lys38(NB-(2-(4-decyl-1-piperazine)acetyl)))hGLP-1(7-
Example 361: (Aib8'35,37 Arg25,26,34, Lys38(N`_(2-(4-dodecyl-1-piperazine)acetyl)))hGLP-
Example 362: (Aib835,37 Arg25'26,34, Lys38(NE-(2-(4_tetradecyl-1-piperazine)acetyl)))hGLP-1(7-38)NH2
Example 363: (Aib8,35,37 Arg25,26,3a Lys38(N`-(2-(4-hexadecyl-1-piperazine)acetyl)))hGLP-
Example 364: (Aib6'35, Arg26,34, Lys36(NE-decanoyl))hGLP-1(7-36)OH
Example 365: (Aib8,35, Lys 25 Arg26,34 Lys36(N`-decanoyl))hGLP-1(7-36)OH
Example 370 (Aib8,35,Arg26,34, Ava37, Ado38)hGLP-1(7-38)NH2
Example 371 (Aib8-35,Arg26,34, Asp37, Ava38, Ado39)hGLP-1(7-39)NH2
Example 372 (Aib8.35,Arg26,34, Aun31)hGLP-1(7-37)NH2
Example 373 (Aib817 35,)hGLP-1(7-36)NH2
Example 374 (Aib8 ,Arg26=34, 13-Ala35, D-Asp37, Ava38, Aun31)hGLP-1(7-39)NH2
Example 375 (Gly8, (3-A1a35)hGLP-1(7-36)NH2
Example 376 (Sera, 13-Ala 35 )hGLP-1 (7-36)NH2
Example 377 (Aib8, GI U22,23, 13-Ala 35)hGLP-1(7-36)NH2
Example 378 (Gly8, Aib35)hGLP-1(7-36)NH2
Example 379 (Aib8, Lys1$, 13-Ala 35)hGLP-1(7-36)NH2 1o Example 380 (Aib8, Leu27, 13-Ala35)hGLP-1(7-36)NH2
Example 381 (Aib8, Lys33, 13-Ala 35)hGLP-1(7-36)NH2
Example 382 (Aib8, Lyst8, Leu27, 13-A1a35)hGLP-1(7-36)NH2
Example 383 (Aib8, D-Arg38)hGLP-1(7-36)NH2
Example 384 (Aib8, /3-Ala35, D-Arg37)hGLP-1(7-37)NH2
Example 385 (Aib8.27, 13-A1a35)hGLP-1(7-36)NH2
Example 386 (Aib8'27, 13-Ala35.37 Arg3B)hGLP-1(7-38)NH2
Example 387 (Aib8,27, 13-Ala35.37, Arg38,39)hGLP-1(7-39)NH2
Example 388 (Aib8, Lys18,27, 13-Ala 35 )hGLP-1 (7-36)NH2
Example 389 (Aib8, Lys27, 13-Ala 35)hGLP-1(7-36)NH2
Example 390 (Aib8, 13-Ala 35, Arg38)hGLP-1 (7-38)NH2
Example 391 (Aib8, Arg26,34, f3_A1a35,)hGLP-1(7-36)NH2
Example 392 (Aib8, D-Arg35)hGLP-1(7-36)NH2
Example 393 (Aib8, 13-Ala35, Arg37 )hGLP-1 (7-37)NH2
Example 394 (Aib8, Phe31, !3-A1a35)hGLP-1(7-36)NH2
Example 395 (Aibe.35, Phe31)hGLP-1(7-36)NH2
Example 396 (Aib8,31, Na131)hGLP-1(7-36)NH2
Example 397 (Aib8.3s Nal28.31)hGLP-1(7-36)NH2
Example 398 (Aib8,35, Arg26,34, Nal31)hGLP-1(7-36)NH2
Example 399 (Aib83s Arg26,34, Phe31)hGLP-1(7-36)NH2
Example 400 (Aib831, Nall 1.31 )hGLP-1(7-36)NH2
Example 401 (Aib8,35, Nal12=31)hGLP-1(7-36)NH2
Example 402 (Aib835 Lys36(N`-decanoyl))hGLP-1(7-36) NH2
Example 403 (Aib8,35, Arg34, Lys26(N`-decanoyl))hGLP-1(7-36)NH2
Example 404 (Aib8.35, Arg26.34, Lys36(N`-dodecanoyl))hGLP-1(7-36)NH2
Example 405 (Aib8,B-AIa35,Ser37(O-decanoyl))hGLP1(7-37)-NH2
Example 406 (Aib8,27, /3-Ala35.37, Arg38, Lys39(NE-octanoyl))hGLP-1(7-39)NH2
Example 407 (AibB, Arg26.31 13-Ala35, Lys37(N`-octanoyl))hGLP-1(7-37)NH2
Example 408 (Aib8, Arg26,34, /3-Ala 35, Lys37(Ns-decanoyl))hGLP-1(7-37)NH2
Example 409 (AibB, Arg26.34, /3-Ala 35, Lys37(NE-tetradecanoyl))hGLP-1(7Example 410 (AibB, Arg26,34/3_AIa35, Lys37(N-dodecanoyl))hGLP-1(7-37)NH2
Example 411 (Aib8, Arg26.34, 13-Ala35, Lys37(N`-dodecanoyl))hGLP-1(8-37)NH2
Physical data for a representative sampling of the compounds exemplified herein are given in Table 1.
Example Mol. Wt. Mol. Wt. Purity
Number Expected MS(ES) (HPLC) 24 3351.8 3352.2 88% 26 3340.17 3340.9 99% 27 3353.81 3353.9 99% 29 3353.81 3353.9 99% 45 3352.6 3352.5 97% 51 3326.74 3326.6 99% 78 3395.81 3395.5 96% 136 3494 3494 99% 364 3523.02 3523.6 99% 365 3580.13 3580.3 95% 369 3677.25 3677 97% 370 3692.28 3692.4 98% 371 3807.37 3807.3 98% 372 3579.11 3579.7 97.90% 373 3337.81 3338.5 94% 374 3779.3 3779.5 94% 375 3297.7 3297.5 99% 376 3327.7 3327.4 98% 377 3398.8 3398.7 97.50% 378 3311.6 3311 93% 379 3366.85 3366.5 97% 380 3309.8 3309.4 99% 381 3354.8 3354.5 97.70% 382 3350.9 3350.3 97.20% 383 3311.73 3310.7 92% 384 3481.95 3481.3 94.30% 385 3281.76 3281.6 98% 386 3509.02 3509.1 99.40% 387 3665.2 3665.1 99% 388 3365.91 3365 97% 389 3324.79 3324.2 95% 390 3539 3539.2 93% 391 3381.74 3381.3 97%
392 3410.89 3409.8 99% 393 3481.95 3481.1 90% 394 3286.76 3286.2 99.20% 395 3300.76 3299.4 93% 396 3350.81 3349.4 99% 397 3400.87 3400.1 99% 398 3406.84 3406.4 99% 399 3356.77 3356.6 99% 400 3384.87 3384.43 94% 401 3400.87 3401.3 99% 402 3466.03 3466.9 97.40% 403 3522.05 3522.06 93% 404 3550.11 3550.2 98% 405 3567.09 99% 406 3763.38 3763.2 95% 407 3636.15 3635.8 99% 408 3664.21 3663.3 99% 409 3720.32 3719.5 99% 410 3692.27 3691.7 99% 411 3555.13 3554.4 99%
TABLE 1 SEQUENCE LISTING
<110> Societe de Conseils de Recherches et D'Applications
Scientifique S.A.S.
<120> ANALOGUES OF GLP-1 <130> 80349-187
<141> 1999-12-07 <150> US 09/206,601 <151> 1998-12-07 <150> US 60/111,255 <151> 1998-12-07 <160> 363
<170> PatentIn Ver. 2.0
<211> 30 <212> PRT <213> Homo sapiens
His Ala Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Arg
<211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus
His Xaa Glu Giy Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gin Ala Ala Lys G_u Phe 11a_; Ala Trp Len Val L 1s Xaa Arg
<211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MOD RES
<223> N-alpha-(4-(2-hydro:yethyl)-1-piterazine-ethanesulfonic acid)-histidine
<221> MOD RES
<223> alpha-aminoisobutyric. acid
<221> MOD RES
<223> alpha-aminoisobutyric acid
<223> this sequence has an ami.dated c-terrrinus
Xaa Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gin Ala Ala Lys Glu Phe 1_e Ala Trp ,eu Val Lys Xaa Arg
<211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MOD RES
<223> N-alpha-(4-(2-hydroxyethvl)-1-pipe razineacetyl) -histidine
<221> MOD RES
<223> alpha-aminoisobutyric acid
<221> MOD RES
<223> alpha-aminoi_sobutv,vr c a,--c id
<223> this sequence has an amidated c-Cerninus
Xaa Xaa Glu GLy Thr She Thr S(nr- Asp Val Ser Ser Tyr Leu Glu Gly
Gin Ala Ala Lys Glu She 1-' A-a Trp Leu Val Lys Xaa Arg
<211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MOD RES
<223> alpha-aminoisobutyric, acid
<221> MOD RES
<223> beta-alanine
<223> this sequence has an amidated c-terminus
His Xaa Glu Gly Thr Phe T'_^Lr Ser Asp Val Ser Ser Tyr Lieu Gin Gly
Gln Ala Ala Lys Glu She I.l(! Ala Trp Len Val Lys Xaa Arg
<211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MOD RES
<223> alpha- amino isobutyric acid
<22-.> MOD RES
<223> alpha-amtnoisobut:yi-ic ac _:3
<221> MOD RES
<223> N-epsilon-tetradecanoyl-lysine
<223> this sequence has an amidated c--erminus
His Xaa Glu Giy Thr Phe Thr Ser Asp Va. Ser Ser Tyr Lou Glu Ply
Gin Ala Ala Arg Glu Phe Ito Ala Top Lei__ Val Arg Xaa Xaa
<211> 30 <212> PRT <213> Artificial Sequence
<223> Description of Artificial Sequence: Mutagen
<221> MOD RES
<223> alpha-aminoisobutyric acid
<221> MOD RES
<223> N-epsilon-tetradecarcyl-lysine
<221> MOD RES <222_> (29) <223> alpha- aminoisobutyric acid
<223> this sequence has an amidated c-term_nus
His Xaa Giu Gly Thr Phe Thr Se-- Asp Val Ser Ser Tyr Leu Glu Gly
Gin Ala Ala Arg Glu Phe Ile Ala Top lec Vai Xaa Xaa Arg
<211> 32 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MOD RES
<223> alpha-aminoisobutyrL.: acid
<22"1> MOD RES
<223> alpha-aminoisobut=~,vr-c acid
<221> MOD RES
<223> alpha-aminoisobutyric acid
<221> MOD RES <222> (32)...(32) <223> Xaa = N-epsilon-tetradecanoyl-lysine
<223> this sequence has a>> amidated terminus
His Xaa Glu Gly Thr Phe T}-,rc Ser Asp Val_ Ser Ser Tyr Leu Glu Gly
Gin Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg Xaa Xaa
<211> 30 <2.12> PRT <213> Artificial Sequence
<223> Mutagen
<221> MOD RES
<223> alpha-aminoisobutyric acid
<221> MOD RES
<223> alpha-aminoisobutyric ac;.d
<221> MOD RES
<223> N epsilon-decanovilysine
<223> this sequence has an amidated n,-terminus
His Xaa Glu Gly Thr Phe Thr Ser. Asp Val Ser Ser Tyr Leu Glu Gly
Gin Ala Ala Arg Glu Phe ile Ala Trp tee Val- Arg Xaa Xaa
<210> 10 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MOD RES
<223> alpha-amino isobutyr acid
<221> MOD RES
<223> alpha-amincisobutyric acid
<221> MOD RES
<222> N-epsilon-dodeca-iesuuLfor.yl-lysine
<223> this sequence has an amidaata terminus <400> 10
His Xaa Glu Gly Thr Phe Torr Ser Asp Val Se r_ Ser Tyr Len Glu Gly
Gin Ala Ala Arg Glu She Lie Ala Trp Lee Val Arg Xaa Xaa
<210> 11 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MOD RES
<223> alpha-aminoisobutyric acid
<221> MOD_RES
<223> alpha-aminoisobutyric ac__d
<22"_> MOD RES
<223> N-epsilon-(2--(4-tetradecv1-l-piperazine)-acetyl) lysine
<223> this sequence has an amidated c-terminus
<400> 11
His Xaa Glu Gly Thr Phe Thl Sr Asp VaL Ser Ser Tyr Leu G1u Gly
Gln Ala Ala Arg Glu Phe I A'_a Trp Lee Val Arq Xaa Xaa
<210> 12 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MOD RES
<223> alpha-aminoisobutyric acid
<221> MOD RES
<223> alpha-aminoisobutyric acid
<221> MOD RES
<223> (1-(4-tetradecyl-pig.,erazine(-acetyl)asparagine
<223> this sequence has an amidated terminus <400> 12
His Xaa Glu Gly Thr Phe TLr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe I'_e Ala Trp :sec; VaArg Xaa Xaa
<210> 13 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MOD RES
<223> alpha-am.inoisobutyr_ic acid
<22"_> MOD RES
<223> alpha-aminoisobutyl.ic ac-S
<221> MOD RES
<223> (1-tetredecylamin>)ecparagine
<223> this sequence has an am_dated c-terminus <400> 13
His Xaa Glu Gly Thr Phe Thr Ser Asp Va- Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu She Ti-- .A,a Trp Lei, Val Arq Xaa Xaa
<210> 14 <211> 31 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MOD RES
<223> alpha-aminoisobutyrlc arid
<221> MOD _RES
<223> alpha-aminoisobutyric acid
<221> MOD RES
<223> N-epsilon-tetradecanoyl.-Lys! ne
<221> MOD RES
<223> beta-alanine
<223> this sequence has an amidated terminus <400> 14
His Xaa Glu Gly Thr.. She 2Ir Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gin Ala Ala Arg Glu She Ile A a Trp Let, Val Arg Xaa Xaa Xaa
<210> 15 <21-> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MOD_RES
<223> alpha-aminoisobutyric a(--.d
<221> MOD RES
<223> alpha-aminoisobutyl'_c acid
<221> MOD RES
<223> N-epsilon-tetradecanoyl-lysine
<223> this sequence has an amiDated c-terminus <400> 15
His Xaa Glu Sly Thr She Thr Ser_ Asp Val Ser Ser Tyr Leu Glu Gly
Gin Ala Ala Arg Glu She Ile Ala Trp Sec Val Arg Xaa Xaa
<210> 16 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MOD RES
<223> 1-amino-l-cyclopen rarecarboxylic acid
<223> this sequence has an and-dated c-terminus <400> -6
His Xaa Glu Gly Thr She Thr Sec Asp `.'a5 Ser Ser Tyr Leu Glu Gly
Gin Ala Ala Lys Glu She _'.e Ala Trp Leu Val Lys Gly Arg
<210> 17 <211_> 31 <212> PRT <213> Artificial Sequence,
<223> Mutagen
<223> this sequence has an amidated c-terminus <400> 17
His Ala Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Arg Gly
<210> 18 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<223> this sequence has an amidated c-terminus <400> 18
His Ala Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Arg
<210> 19 <211> 32 <212> PRT <213> Artificial Sequence
<223> Mutagen
<223> this sequence has an amidated c-terminus <400> 19
His Ala Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Arg Giy Arg
<210> 20 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> N,N-tetramethylamidinohistidine
<223> this sequence has an amidated c-terminus <400> 20
Xaa Ala Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Arg
<210> 21 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> [125I]-3-iodotyrosine
<223> this sequence has an amidated c-terminus <400> 21
His Ala Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Arg
<210> 22 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 22
His Ala Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Xaa Arg
<210> 23 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MOD RES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 23
His Ala Glu Gly Thr Phe Phi Sec Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Lys Glu Phe Ie Ala Trp Lee Sal Lys Xaa Arg
<210> 24 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MOD RES
<223> N alpha methylhistiaine<22C>
<221> MOD RES
<223> alpha-aminoi.sobutiric: acid
<221> MOD RES
<223> alpha-aminoisobutyl._c acid
<223> this sequence has art amidated c-terminus <400> 24
Xaa Xaa Glu Gly Thr Phe Thy Ser Asp Val Sec Ser Tyr Leu Glu Gly
Gln Ala Ala Lys Glu Phe III. Gle Trp Let- Val Lis Xaa Arg
<210> 25 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MOD RES
<223> N-alpha-met.hylhistidine
<221> MOD RES
<223> alpha-aminoi.sobutyric acid
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated --terminus <40C> 25
Xaa Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Lys Glu Phe IIeAI a Tcp Leu Val Lys Xaa Arg
<21C> 26 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MOD RES
<223> N-alpha-methylhistidine
<221> MODRES
<223> alpha-amirioisobutyr acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated terminus <40C> 26
Xaa Xaa Glu Gly Thr Phe Ph- Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Gin Phe Ile Ala Trp1Leu Val Arg Xaa Arg
<210> 27 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MOD RES
<223> N-alpha-methylhistidine
<221> MOD RES
<223> alpha -aminoisobutyric acid
<221> MOD RES
<223> beta-alanine
<223> this sequence has a> amidated c-terminus <400> 27
Xaa Xaa Glu Gly Thr She T1--r Ser Asp Val Sec Ser Tyr Leu Glu Gly
Gin Ala Ala Arg Glu She Ile Ala Trp 'i_,ee Vol Arg Xaa Arg
<210> 28 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MOD RES
<223> alpha-aminoisobutyric acid
<221> MOD RES
<223> 1-amino-l-cyclohexanecarboxylic acid
<223> this sequence has an amidated c-terminus <400> 28
His Xaa Glu Gly Thr Phe Th Ser Asp Va_ Ser Sec Tyr Leu Glu Gly
Gin Ala Ala Lys Gin Phe Ile Ala Tap Leu Val Lys Xaa Arg
<210> 29 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MOD RES
<223> alpha-aminoisobutyric acid
<221> MOD RES
<223> 1 amino l-cyclohekanecarboxyli:~ acic
<223> this sequence has an amidated c-terrr_cnus <400> 29
His Xaa Glu Gly Thr She Thr Se- Asp Val Ser Ser Tyr Lea Glu Gly
Gin Ala Ala Lys Glu She :LIE Ala Trp den Val Lys Xaa Arg
<21.0> 30 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MOD RES
<223> alpha-aminoisobutyric acid
<221> MOD RES
<223> i-amino-l-cyclohexanecarboxylic: acid
<221> MOD RES
<223> alpha-aminoisobutyric acid
<223> this sequence has ar; am.idated :-terminus
<403> 30
His Xaa Glu Gly Thr Phe TSLI See Asp Va] Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Lys GIu Phe IIe Ala Trp Sac Val Lys Xaa Arg
<213> 31 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MOD RES
<223> alpha-aminoisobutyl:r_ic acid
<221> MOD RES
<223> 1-amino-l-cyclohexanecarboxylic acid
<221> MOD RES
<223> alpha-aminoisobutyr_e acid
<223> this sequence has an amidated (c-terminus <400> 31
His Xaa Glu Gly Thr Phe The Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gin Ala Ala Lys Glu Phe Ile Ala Trp Xaa Val- Lys Xaa Arg
<210> 32 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MOD RES
<223> alpha-aminoisobutyric acid
<221> MOD RES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated terminus <403> 32
His Xaa Glu Gly Th.r She Its Ser Asp Va] Sec Ser Tyr Leu Glu Gly
Glu Ala Ala Lys Glu She Ile Ala Trp tee VaI Lys Xaa Arg
<210> 33 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MOD RES
<223> alpha-amincisobutyc.c acid
<22:1> MOD RES
<223> alpha-aminoisobutyric acid
<221> MOD RES
<223> alpha-aminoisobutyric acrid
<223> this sequence has an amidated termi mss <400> 33
His Xaa Glu Gly Thr She Shr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Glri Xaa Ala Lys Glu She -1e Ala Ti-.-p Leu Val Lys Xaa Arg
<210> 34 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<22_> MOD RES
<223> alpha-aminoisobutyric ac-_d
<22"1> MOD RES
<223> alpha-aminoisobutyric acid
<221> MOD RES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated terminus <400> 34
His Xaa G1-u Sly Thr Phe Thy Ser Asp `Jal Sec Ser Tyr Leu Glu Gly
Gin Ala Ala Lys Glu.i Phe Ile Xaa Trp Leu Val Lys Xaa Arg
<210> 35 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MOD RES
<223> alpha-amincisobutyr_c acid
<221> MOD RES
<223> alpha-aminoisobutyl-i_c acid
<221> MOD RES
<223> alpha-aminoisobutyric acid
<223> this sequence has :,n am-l'-dated <400> 35
His Xaa Glu Gly Thr She ~h Her Asp ?al Ser Ser Tyr Leu Glu Gly
Gin Ala Xaa Lys Glu Phe IIE Ala Trp Lea Val Lys Xaa Arg
<210> 36 <21"_> 30 <212> PRT <213> Artificial Sequenic i
<223> Mutagen
<221> MOD RES
<223> alpha-aminoisobutyric acid
<221> MOD RES
<223> 1-amino-l-cyclohexarecarboxyli>- acid
<221> MOD RES
<223> 1-amino-l-cycIohexarecarboxyi.ic acid
<221> MOD RES
<223> alpha-aminoisobutyl.ic acid
<223> this sequence has an am_idated c-terminus <400> 36
His Xaa Glu Gly Thr She Thi Ser Asp Xaa Ser Ser Tyr Xaa Glu Gly
Gin Ala Ala Lys Glu She L.F Ala Trp Leu Val `Oys Xaa Arg
<210> 37 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MOD_RES
<223> alpha-am noisobutyr.:i.a acid
<221> MOD RES
<223> 1 amino l cyclohexanecarboxyii:: acid
<221> MOD RES
<223> 1-amino-l-cyclohexanecarboxylic acid
<221> MOD RES
<223> 1-amino-l-cyclohexanecarboxylic acid
<221> MOD RES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amicated -terminus <400> 37
His Xaa Glu Gly Thr Phe Thi Ser Asp San Ser Ser Tyr Leu Glu Gly
Gin Ala Ala Lys Glu Phe Tan Ala Trp Xan Val Lys Xaa Arg
<210> 38 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MOD RES
<223> alpha-aminoisobutyric acid
<221> MOD RES
<223> 1-amino-l-cyclohexa1-1ecarwhoxylic acid
<221> MOD RES
<223> 1-amino-l-cyclohexanecartoxyiic acid
<221> MOD RES
<223> alpha-aminoisobutyrir- acid
<223> this sequence has an amidated c-terminus <40C> 38
His Xaa Glu Gly Th.r Phe TI_r Ser. Asp `Ja_ Ser Ser Tyr Xaa Glu Gly
Gln Ala Ala Lys Glu The LLEe Ala Tap San Val Lys Xaa Arg
<210> 39 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MOD RES
<223> alpha-aminoisobu-yr_1_c acid
<221> MOD RES
<223> 1 amino 1 cyclohexanecarboxylic acid
<221> MOD RES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terrrinus <400> 39
His Xaa Glu Gly The She Thr Ser Asp Val Ser Ser Tyr Xaa Glu Gly
Gln Ala Ala Lys Glu She Ie Ala Tr:p ijen Gal Lys Xaa Arg
<210> 40 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MOD RES
<223> alpha-anLnoisobutyr c acid
<221> MOD RES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidate-d terminus <400> 40
His Xaa Glu Gly Thr She :ter Ser Asp Gal Ser Ser Tyr Leu Glu Gly
Gln Ala Lys Lys Glu She ' 1e A--ca Trp Len Val Lys Xaa Arg
<210> 41 <21"1> 30 <212> PRT
<213> Artificial Sequence
<223> Mutagen
<221> MOD RES
<223> alpha-aminoisobutyric acid
<221> MOD RES
<223> 1-amino l cyclohexanecarboxylic acid
<221> MOD RES
<223> alpha- aminoisobutyl.-~i_c acid
<221> MOD RES
<223> alpha-aminoisobutyl-(- acid
<223> this sequence has an amidated (--terminus <400> 41
His Xaa Glu Gly Thr Phe Thr Ser Asp `1<1 Set- Ser Tyr Xaa Glu Gly
Gin Xaa Ala Lys Glu Phe I1 Ala Trp Sec Val Lys Xaa Arg
<210> 42 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MOD RES
<223> alpha-amino isobutyr1 c acid
<221> MOD RES
<223> 1-amino-1-cyclohexanecarboxylic-c acid
<221> MOD RES
<223> 1-amino-l-cyclohexanecardoxylic acid
<221> MOD RES
<223> alpha-aminoisobutv;r.ic acid
<223> this sequence has a> arnidated terminus <400> 42
His Xaa Glu Gly Thr Phe Tri See Asp Val Ser Ser Tyr Lea Glu Gly
Gin Ala Ala Lys Glu Phe Xaa Ala Trp Xaa, Val Lys Xaa Arg
<210> 43 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MOD RES
<223> alpha-aminoisobutyl:ic acid
<221> MOD RES
<223> alpha-aminoisobutyr_=i_c: acid
<221> MOD RES
<223> 1-amino-l-cyr_lohexanecer_boxYlic a~,id
<221> MOD RES
<223> 1-amino l cyclohexanecarOoxyli, acid
<221> MODRES
<223> alpha-aminoisobutyrii_c acid
<223> this sequence has an arridated t rmi.nus <400> 43
His Xaa Glu Gly Thr She Shi Ser Asp >al Sec Ser Tyr Leu Glu Sly
Gin Xaa Ala Lys Glu She Sac Ala Trp _taa Val Lys Xaa Arg
<210> 44 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 1-amino-l-cyclohexanecarboxylic acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 44
His Xaa Glu Gly Thr Xaa Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Xaa Arg
<210> 45 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> cyclohexylalanine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus
<400> 45
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Xaa Glu Gly
Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Xaa Arg
<210> 46 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 1-amino-l-cyclohexanecarboxylic acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 46
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Xaa Lys Xaa Arg
<210> 47 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 1-amino-l-cyclohexanecarboxylic acid
<221> MODRES
<223> 1-amino-l-cyclohexanecarboxylic acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 47
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Xaa Glu Gly
Gln Ala Ala Lys Glu Phe Ile Ala Trp Xaa Val Lys Xaa Arg
<210> 48 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 1-amino-l-cyclohexanecarboxylic acid
<221> MODRES
<223> 1-amino-l-cyclohexanecarboxylic acid
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 48
His Xaa Glu Gly Thr Phe Thr Ser Asp Xaa Ser Ser Tyr Xaa Glu Gly
Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Xaa Arg
<210> 49 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> beta-alanine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 49
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Xaa
Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Xaa Arg
<210> 50 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus
<400> 50
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Xaa
Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Xaa Arg
<210> 51 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 1-amino-l-cyclohexanecarboxylic acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 51
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Glu Ala Ala Lys Glu Phe Ile Ala Trp Xaa Val Lys Xaa Arg
<210> 52 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 1-amino-l-cyclohexanecarboxylic acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 52
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Glu Xaa Ala Lys Glu Phe Ile Ala Trp Xaa Val Lys Xaa Arg
<210> 53 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 1-amino-l-cyclohexanecarboxylic acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus
<400> 53
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Glu Xaa Xaa Lys Glu Phe Ile Ala Trp Xaa Val Lys Xaa Arg
<210> 54 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 1-amino-l-cyclohexanecarboxylic acid
<221> MODRES
<223> 1-amino-l-cyclohexanecarboxylic acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 1-amino-l-cyclohexanecarboxylic acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 54
His Xaa Glu Gly Thr Phe Thr Ser Asp Xaa Ser Ser Tyr Xaa Glu Gly
Glu Xaa Xaa Lys Glu Phe Ile Ala Trp Xaa Val Lys Xaa Arg
<210> 55 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 1-amino-l-cyclohexanecarboxylic acid
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 55
His Xaa Glu Gly Thr Phe Thr Ser Asp Val. Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Lys Glu Phe Ile Ala Trp Xaa Val Lys Xaa Arg
<210> 56 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 1-amino-l-cyclopentanecarboxylic acid
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus
<400> 56
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Lys Glu Phe Ile Ala Trp Xaa Val Lys Xaa Arg
<210> 57 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 57
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Glu Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Xaa Arg
<210> 58 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 58
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Xaa Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Xaa Arg
<210> 59 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 59
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Lys Glu Phe Ile Xaa Trp Leu Val Lys Xaa Arg
<210> 60 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 60
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Xaa Lys Glu Phe Ile Ala Trp Leu Val Lys Xaa Arg
<210> 61 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 1-amino-l-cyclohexanecarboxylic acid
<221> MODRES
<223> 1-amino-l-cyclohexanecarboxylic acid
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 61
His Xaa Glu Gly Thr Phe Thr Ser Asp Xaa Ser Ser Tyr Xaa Glu Gly
Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Xaa Arg
<210> 62 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 1-amino-l-cyclohexanecarboxylic acid
<221> MODRES
<223> 1-amino-l-cyclohexanecarboxylic acid
<221> MODRES
<223> 1-amino-l-cyclohexanecarboxylic acid
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 62
His Xaa Glu Gly Thr Phe Thr Ser Asp Xaa Ser Ser Tyr Leu Glu Gly
Gin Ala Ala Lys Glu Phe Xaa Ala Trp Xaa Val Lys Xaa Arg
<210> 63 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 1-amino-l-cyclohexanecarboxylic acid
<221> MOD_RES
<223> 1-amino-l-cyclohexanecarboxylic acid
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 63
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Xaa Glu Gly
Gln Ala Ala Lys Glu Phe Ile Ala Trp Xaa Val Lys Xaa Arg
<210> 64 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 1-amino-l-cyclohexanecarboxylic acid
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 64
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Xaa Glu Gly
Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Xaa Arg
<210> 65 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 65
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Lys Lys Glu Phe Ile Ala Trp Leu Val Lys Xaa Arg
<210> 66 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> i-amino-i-cyclohexanecarboxylic acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 66
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Xaa Glu Gly
Gln Xaa Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Xaa Arg
<210> 67 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 1-amino-i-cyclohexanecarboxylic acid
<221> MODRES
<223> 1-amino-l-cyclohexanecarboxylic acid
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 67
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Lys Glu Phe Xaa Ala Trp Xaa Val Lys Xaa Arg
<210> 68 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MOD_RES
<223> 1-amino-l-cyclohexanecarboxylic acid
<221> MODRES
<223> 1-amino-l-cyclohexanecarboxylic acid
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 68
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Xaa Ala Lys Glu Phe Xaa Ala Trp Xaa Val Lys Xaa Arg
<210> 69 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 1-amino-l-cyclohexanecarboxylic acid
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 69
His Xaa Glu Gly Thr Xaa Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Xaa Arg
<210> 70 <211> 30 <212> PRT
<213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> cyclohexylalanine
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 70
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Xaa Glu Gly
Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Xaa Arg
<210> 71 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 1-amino-l-cyclohexanecarboxylic acid
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus
<400> 71
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Xaa Lys Xaa Arg
<210> 72 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 1-amino-l-cyclohexanecarboxylic acid
<221> MODRES
<223> 1-amino-l-cyclohexanecarboxylic acid
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 72
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Xaa Glu Gly
Gln Ala Ala Lys Glu Phe Ile Ala Trp Xaa Val Lys Xaa Arg
<210> 73 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> beta-alanine
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 73
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Xaa
Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Xaa Arg
<210> 74 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 74
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Xaa
Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Xaa Arg
<210> 75 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 1-amino-l-cyclohexanecarboxylic acid
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 75
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Glu Ala Ala Lys Glu Phe Ile Ala Trp Xaa Val Lys Xaa Arg
<210> 76 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 1-amino-i-cyclohexanecarboxylic acid
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus
<400> 76
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Glu Xaa Ala Lys Glu Phe Ile Ala Trp Xaa Val Lys Xaa Arg
<210> 77 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 1-amino-l-cyclohexanecarboxylic acid
<221> MODRES
<223> N-epsilon-octanoyl-lysine
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 77
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Glu Xaa Ala Lys Glu Phe Ile Ala Trp Xaa Val Xaa Xaa Arg
<210> 78 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 1-amino-l-cyclohexanecarboxylic acid
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 78
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Glu Xaa Xaa Lys Glu Phe Ile Ala Trp Xaa Val Lys Xaa Arg
<210> 79 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 1-amino-l-cyclohexanecarboxylic acid
<221> MODRES
<223> 1-amino-l-cyclohexanecarboxylic acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 1-amino-l-cyclohexanecarboxylic acid
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 79
His Xaa Glu Gly Thr Phe Thr Ser Asp Xaa Ser Ser Tyr Xaa Glu Gly
Glu Xaa Xaa Lys Glu Phe Ile Ala Trp Xaa Val Lys Xaa Arg
<210> 80 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 80
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg
<210> 81 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 81
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg
<210> 82 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 82
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg
<210> 83 <211> 30 <212> PRT
<213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 83
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg
<210> 84 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> beta-alanine
<221> MODRES
<223> N-epsilon-tetradecanoyl-lysine <400> 84
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Xaa
<210> 85 <211> 31 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-tetradecanoyl-lysine <400> 85
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Xaa Gly
<210> 86 <211> 31 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-tetradecanoyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid <400> 86
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Xaa Xaa
<210> 87 <211> 32 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-tetradecanoyl-lysine <400> 87
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg Xaa Xaa
<210> 88 <211> 32 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MOD_RES
<223> beta-alanine
<221> MODRES
<223> N-epsilon-tetradecanoyl-lysine <400> 88
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg Xaa Xaa
<210> 89 <211> 32 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-tetradecanoyl-lysine <400> 89
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg Gly Xaa
<210> 90 <211> 31 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-tetradecanoyl-lysine
<221> MODRES
<223> beta-alanine <400> 90
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Gly Xaa Xaa
<210> 91 <211> 31 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-tetradecanoyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid <400> 91
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Gly Xaa Xaa
<210> 92 <211> 31 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 12-aminododecanoic acid <400> 92
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg Xaa
<210> 93 <211> 31 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 12-aminododecanoic acid
<223> this sequence has an amidated c-terminus <400> 93
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg Xaa
<210> 94 <211> 32 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-tetradecanoyl-lysine <400> 94
His Xaa Glu Gly Thr Phe Thr Ser Asp Val. Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Gly Arg Xaa Xaa
<210> 95 <211> 32 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> beta-alanine
<221> MODRES
<223> N-epsilon-tetradecanoyl-lysine <400> 95
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Gly Arg Xaa Xaa
<210> 96 <211> 32 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-octanoyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 96
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Gly Arg Xaa Xaa
<210> 97 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-tetradecanoyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 97
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Xaa Glu Phe Ile Ala Trp Leu Val Lys Xaa Arg
<210> 98 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-hexadecanoyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 98
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Xaa Glu Phe Ile Ala Trp Leu Val Lys Xaa Arg
<210> 99 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-octanoyl-lysine
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus
<400> 99
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Xaa Glu Phe Ile Ala Trp Leu Val Lys Xaa Arg
<210> 100 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-tetradecanoyl-lysine
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 100
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Xaa Glu Phe Ile Ala Trp Leu Val Lys Xaa Arg
<210> 101 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-hexaxecanoyl-lysine
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 101
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Xaa Glu Phe Ile Ala Trp Leu Val Lys Xaa Arg
<210> 102 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-octanoyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 102
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Xaa Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg
<210> 103 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-tetradecanoyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 103
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Xaa Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg
<210> 104 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-hexadecanoyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 104
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Xaa Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg
<210> 105 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-decanoyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 105
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Xaa Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg
<210> 106 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-octanoyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 106
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Lys Xaa Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg
<210> 107 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-tetradecanoyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 107
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Lys Xaa Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg
<210> 108 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-hexadecanoyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 108
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Lys Xaa Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg
<210> 109 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-octanoyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 109
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Xaa Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg
<210> 110 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MOD_RES
<223> N-epsilon-tetradecanoyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 110
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Xaa Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg
<210> 111 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-hexadecanoyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 111
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Xaa Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg
<210> 112 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-decanoyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 112
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Xaa Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg
<210> 113 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-octanoyl-lysine
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 113
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Xaa Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg
<210> 114 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-tetradecanoyl-lysine
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 114
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Xaa Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg
<210> 115 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-hexadecanoyl-lysine
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus
<400> 115
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Xaa Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg
<210> 116 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-decanoyl-lysine
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 116
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Xaa Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg
<210> 117 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-octanoyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 117
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Xaa Xaa Arg
<210> 118 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-tetradecanoyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 118
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Xaa Xaa Arg
<210> 119 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-hexadecanoyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 119
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Xaa Xaa Arg
<210> 120 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-octanoyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 120
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Xaa Xaa Arg
<210> 121 <211> 30 <212> PRT <213> Artificial Sequence
-ill<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-hexadecanoyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 121
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Xaa Xaa Arg
<210> 122 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-decanoyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 122
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Xaa Xaa Arg
<210> 123 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MOD_RES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-octanoyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 123
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Xaa Xaa Arg
<210> 124 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-tetradecanoyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 124
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Xaa Xaa Arg
<210> 125 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-hexadecanoyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 125
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Xaa Xaa Arg
<210> 126 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MOD_RES
<223> N-epsilon-decanoyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 126
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Xaa Xaa Arg
<210> 127 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-octanoyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 127
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Lys Arg Glu Phe Ile Ala Trp Leu Val Xaa Xaa Arg
<210> 128 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-tetradecanoyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 128
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Lys Arg Glu Phe Ile Ala Trp Leu Val Xaa Xaa Arg
<210> 129 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-hexadecanoyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 129
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Lys Arg Glu Phe Ile Ala Trp Leu Val Xaa Xaa Arg
<210> 130 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-octanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 130
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Xaa Xaa
<210> 131 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-tetradecanoyl-lysine
<223> this sequence has an amidated c-terminus
<400> 131
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Xaa Xaa
<210> 132 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-hexadecanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 132
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Xaa Xaa
<210> 133 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-octanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 133
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Lys Xaa Xaa
<210> 134 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-tetradecanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 134
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Lys Xaa Xaa
<210> 135 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-hexadecanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 135
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Lys Xaa Xaa
<210> 136 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-octanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 136
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Xaa
<210> 137 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-hexadecanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 137
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Xaa
<210> 138 <211> 32 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-octanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 138
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg Gly Xaa
<210> 139 <211> 32 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-decanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 139
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg Gly Xaa
<210> 140 <211> 32 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-tetradecanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 140
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg Gly Xaa
<210> 141 <211> 32 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-hexadecanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 141
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg Gly Xaa
<210> 142 <211> 32 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MOD_RES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-octanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 142
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg Xaa Xaa
<210> 143 <211> 32 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-decanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 143
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg Xaa Xaa
<210> 144 <211> 32 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-tetradecanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 144
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg Xaa Xaa
<210> 145 <211> 32 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-hexadecanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 145
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg Xaa Xaa
<210> 146 <211> 32 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-octanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 146
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg Xaa Xaa
<210> 147 <211> 32 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-decanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 147
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg Xaa Xaa
<210> 148 <211> 32 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MOD_RES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-hexadecanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 148
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg Xaa Xaa
<210> 149 <211> 32 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-octanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 149
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg Xaa Xaa
<210> 150 <211> 32 <212> PRT
<213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-decanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 150
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg Xaa Xaa
<210> 151 <211> 32 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-tetradecanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 151
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg Xaa Xaa
<210> 152 <211> 32 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-hexadecanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 152
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Giu Phe Ile Ala Trp Leu Val Arg Xaa Arg Xaa Xaa
<210> 153 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-octanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 153
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Lys Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Xaa
<210> 154 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-tetradecanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 154
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Lys Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Xaa
<210> 155 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-hexadecanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 155
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Lys Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Xaa
<210> 156 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-octanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 156
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Xaa
<210> 157 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-tetradecanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 157
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Xaa
<210> 158 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MOD_RES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-hexadecanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 158
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Xaa
<210> 159 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-decanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 159
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Xaa
<210> 160 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-octanoyl-lysine
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 160
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Xaa Xaa Arg
<210> 161 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-tetradecanoyl-lysine
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 161
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Xaa Xaa Arg
<210> 162 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-hexadecanoyl-lysine
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 162
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Xaa Xaa Arg
<210> 163 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 1-amino-l-cyclohexanecarboxylic acid
<221> MODRES
<223> N-epsilon-octanoyl-lysine
<221> MOD_RES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 163
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Lys Glu Phe Ile Ala Trp Xaa Val Xaa Xaa Arg
<210> 164 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-octanoyl-lysine
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 164
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Glu Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Xaa Xaa Arg
<210> 165 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 1-amino-l-cyclohexanecarboxylic acid
<221> MODRES
<223> N-epsilon-octanoyl-lysine
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 165
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Glu Ala Ala Lys Glu Phe Ile Ala Trp Xaa Val Xaa Xaa Arg
<210> 166 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-octanoyl-lysine
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 166
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Xaa Xaa Arg
<210> 167 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-tetradecanoyl-lysine
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 167
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Xaa Xaa Arg
<210> 168 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-hexadecanoyl-lysine
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus
<400> 168
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Xaa Xaa Arg
<210> 169 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-decanoyl-lysine
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 169
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Xaa Xaa Arg
<210> 170 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-octanoyl-lysine
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 170
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Xaa Xaa Arg
<210> 171 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-tetradecanoyl-lysine
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 171
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Xaa Xaa Arg
<210> 172 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-hexadecanoyl-lysine
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 172
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Xaa Xaa Arg
<210> 173 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-decanoyl-lysine
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 173
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Xaa Xaa Arg
<210> 174 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-octanoyl-lysine
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 174
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Lys Arg Glu Phe Ile Ala Trp Leu Val Xaa Xaa Arg
<210> 175 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-tetradecanoyl-lysine
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 175
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Lys Arg Glu Phe Ile Ala Trp Leu Val Xaa Xaa Arg
<210> 176 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-hexadecanoyl-lysine
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 176
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Lys Arg Glu Phe Ile Ala Trp Leu Val Xaa Xaa Arg
<210> 177 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> beta-alanine
<221> MODRES
<223> N-epsilon-octanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 177
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Xaa Xaa
<210> 178 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> beta-alanine
<221> MODRES
<223> N-epsilon-tetradecanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 178
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Xaa Xaa
<210> 179 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MOD_RES
<223> beta-alanine
<221> MODRES
<223> N-epsilon-hexadecanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 179
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Xaa Xaa
<210> 180 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> beta-alanine
<221> MODRES
<223> N-epsilon-octanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 180
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Lys Xaa Xaa
<210> 181 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> beta-alanine
<221> MODRES
<223> N-epsilon-tetradecanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 181
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Lys Xaa Xaa
<210> 182 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> beta-alanine
<221> MODRES
<223> N-epsilon-hexadecanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 182
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Lys Xaa Xaa
<210> 183 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> beta-alanine
<221> MODRES
<223> N-epsilon-octanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 183
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Xaa
<210> 184 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> beta-alanine
<221> MODRES
<223> N-epsilon-tetradecanoyl-lysine
<223> this sequence has an amidated c-terminus
<400> 184
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Xaa
<210> 185 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> beta-alanine
<221> MODRES
<223> N-epsilon-hexadecanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 185
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Xaa
<210> 186 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> beta-alanine
<221> MODRES
<223> N-epsilon-decartoyl-lysine
<223> this sequence has an amidated c-terminus <400> 186
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Xaa
<210> 187 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> beta-alanine
<221> MODRES
<223> N-epsilon-octanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 187
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Lys Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Xaa
<210> 188 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> beta-alanine
<221> MODRES
<223> N-epsilon-tetradecanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 188
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Lys Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Xaa
<210> 189 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> beta-alanine
<221> MODRES
<223> N-epsilon-hexadecanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 189
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Lys Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Xaa
<210> 190 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> beta-alanine
<221> MODRES
<223> N-epsilon-octanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 190
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Xaa
<210> 191 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> beta-alanine
<221> MODRES
<223> N-epsilon-tetradecanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 191
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Xaa
<210> 192 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> beta-alanine
<221> MODRES
<223> N-epsilon-hexadecanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 192
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Xaa
<210> 193 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> beta-alanine
<221> MODRES
<223> N-epsilon-decanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 193
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Xaa
<210> 194 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-octanoyl-lysine
<221> MODRES
<223> 1-amino-l-cylohexanecarboxylic acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 194
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Xaa Glu Phe Ile Ala Trp Xaa Val Arg Xaa Arg
<210> 195 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MOD_RES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-tetradecanoyl-lysine
<221> MODRES
<223> 1-amino-l-cylohexanecarboxylic acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 195
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Xaa Glu Phe Ile Ala Trp Xaa Val Arg Xaa Arg
<210> 196 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-hexadecanoyl-lysine
<221> MODRES
<223> 1-amino-l-cylohexanecarboxylic acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus
<400> 196
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Xaa Glu Phe Ile Ala Trp Xaa Val Arg Xaa Arg
<210> 197 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 1-amino-l-cylohexanecarboxylic acid
<221> MODRES
<223> N-epsilon-octanoyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 197
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Lys Glu Phe Ile Ala Trp Xaa Val Xaa Xaa Arg
<210> 198 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 1-amino-l-cylohexanecarboxylic acid
<221> MODRES
<223> N-epsilon-tetra.decanoyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 198
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Lys Glu Phe Ile Ala Trp Xaa Val Xaa Xaa Arg
<210> 199 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 1-amino-l-cylohexanecarboxylic acid
<221> MODRES
<223> N-epsilon-hexadecanoyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus
<400> 199
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Lys Glu Phe Ile Ala Trp Xaa Val Xaa Xaa Arg
<210> 200 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 1-amino-i-cylohexanecarboxylic acid
<221> MODRES
<223> N-epsilon-octanoyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 200
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Xaa Val Xaa Xaa Arg
<210> 201 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 1-amino-l-cylohexanecarboxylic acid
<221> MODRES
<223> N-epsilon-tetra.decanoyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 201
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Xaa Val Xaa Xaa Arg
<210> 202 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> i-amino-l-cylohexanecarboxylic acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-octanoyl-lysine
<223> this sequence has an amidated c-terminus
<400> 202
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Lys Glu Phe Ile Ala Trp Xaa Val Lys Xaa Xaa
<210> 203 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 1-amino-l-cylohexanecarboxylic acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-tetradecanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 203
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Lys Glu Phe Ile Ala Trp Xaa Val Lys Xaa Xaa
<210> 204 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 1-amino-l-cylohexanecarboxylic acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-hexad.ecanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 204
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Lys Glu Phe Ile Ala Trp Xaa Val Lys Xaa Xaa
<210> 205 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 1-amino-l-cylohexanecarboxylic acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-octanoyl-lysine
<223> this sequence has an amidated c-terminus
<400> 205
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Xaa Val Lys Xaa Xaa
<210> 206 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 1-amino-l-cylohexanecarboxylic acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-tetradecanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 206
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Xaa Val Lys Xaa Xaa
<210> 207 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 1-amino-l-cyloh.exanecarboxylic acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-hexad.ecanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 207
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Xaa Val Lys Xaa Xaa
<210> 208 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 1-amino-l-cylohexanecarboxylic acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-octanoyl-lysine
<223> this sequence has an amidated c-terminus
<400> 208
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Xaa Val Arg Xaa Xaa
<210> 209 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 1-amino-l-cylohexanecarboxylic acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-decanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 209
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Xaa Val Arg Xaa Xaa
<210> 210 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 1-amino-l-cyloh.exanecarboxylic acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-tetradecanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 210
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Xaa Val Arg Xaa Xaa
<210> 211 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 1-amino-l-cylohexanecarboxylic acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-hexadecanoyl-lysine
<223> this sequence has an amidated c-terminus
<400> 211
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Xaa Val Arg Xaa Xaa
<210> 212 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-octanoyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 212
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Xaa Ala Xaa Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg
<210> 213 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-tetradecanoyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 213
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Xaa Ala Xaa Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg
<210> 214 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-hexadecanoyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus
<400> 214
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Xaa Ala Xaa Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg
<210> 215 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-octanoyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 215
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Xaa Ala Arg Glu Phe Ile Ala Trp Leu Val Xaa Xaa Arg
<210> 216 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-tetradecanoyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 216
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Xaa Ala Arg Glu Phe Ile Ala Trp Leu Val Xaa Xaa Arg
<210> 217 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-hexadecanoyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus
<400> 217
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Xaa Ala Arg Glu Phe Ile Ala Trp Leu Val Xaa Xaa Arg
<210> 218 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-octanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 218
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Xaa Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Xaa
<210> 219 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-tetradecanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 219
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Xaa Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Xaa
<210> 220 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-hexadecanoyl-lysine
<223> this sequence has an amidated c-terminus
<400> 220
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Xaa Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Xaa
<210> 221 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 1-amino-l-cylohexanecarboxylic acid
<221> MODRES
<223> N-epsilon-hexadecanoyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 221
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Glu Xaa Ala Lys Glu Phe Ile Ala Trp Xaa Val Xaa Xaa Arg
<210> 222 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-octanoyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 222
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Glu Ala Ala Xaa Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg
<210> 223 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-tetradecanoyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 223
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Glu Ala Ala Xaa Glu P.1-le Ile Ala Trp Leu Val Arg Xaa Arg
<210> 224 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-hexadecanoyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 224
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Glu Ala Ala Xaa Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg
<210> 225 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-octanoyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus
<400> 225
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Glu Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Xaa Xaa Arg
<210> 226 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MOD RES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 1-amino-l-cylohexanecarboxylic acid
<221> MODRES
<223> N-epsilon-octanoyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 226
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Glu Ala Ala Lys Glu Phe Ile Ala Trp Xaa Val Xaa Xaa Arg
<210> 227 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-octanoyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 227
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Glu Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Xaa Xaa Arg
<210> 228 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-tetradecanoyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 228
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Glu Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Xaa Xaa Arg
<210> 229 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-hexadecanoyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 229
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Glu Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Xaa Xaa Arg
<210> 230 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-octanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 230
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Glu Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Xaa Xaa
<210> 231 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-tetradecanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 231
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Glu Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Xaa Xaa
<210> 232 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-hexadecanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 232
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Glu Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Xaa Xaa
<210> 233 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-octanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 233
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Glu Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Xaa
<210> 234 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MOD_RES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-tetradecanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 234
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Glu Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Xaa
<210> 235 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-hexadecanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 235
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Glu Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Xaa
<210> 236 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-octanoyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 236
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Xaa Glu Phe Ile Xaa Trp Leu Val Arg Xaa Arg
<210> 237 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-tetradecanoyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 237
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Xaa Glu Phe Ile Xaa Trp Leu Val Arg Xaa Arg
<210> 238 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-hexadecanoyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 238
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Xaa Glu Phe Ile Xaa Trp Leu Val Arg Xaa Arg
<210> 239 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-octanoyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 239
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Xaa Trp Leu Val Xaa Xaa Arg
<210> 240 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-tetradecanoyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus
<400> 240
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Xaa Trp Leu Val Xaa Xaa Arg
<210> 241 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-hexadecanoyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 241
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Xaa Trp Leu Val Xaa Xaa Arg
<210> 242 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-octanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 242
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Xaa Trp Leu Val Arg Xaa Xaa
<210> 243 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-tetradecanoyl-lysine
<223> this sequence has an amidated c-terminus
<400> 243
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Xaa Trp Leu Val Arg Xaa Xaa
<210> 244 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-hexadecanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 244
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Xaa Trp Leu Val Arg Xaa Xaa
<210> 245 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 1-amino-l-cyclohexanecarboxylic acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-octanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 245
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Glu Ala Ala Lys Glu Phe Ile Ala Trp Xaa Val Lys Xaa Xaa
<210> 246 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 1-amino-l-cyclohexanecarboxylic acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-tetradecanoyl-lysine
<223> this sequence has an amidated c-terminus
<400> 246
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Glu Ala Ala Lys Glu Phe Ile Ala Trp Xaa Val Lys Xaa Xaa
<210> 247 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 1-amino-l-cyclohexanecarboxylic acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-hexadecanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 247
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Glu Ala Ala Lys Glu Phe Ile Ala Trp Xaa Val Lys Xaa Xaa
<210> 248 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 1-amino-l-cyclohexanecarboxylic acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-octanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 248
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Glu Ala Ala Arg Glu Phe Ile Ala Trp Xaa Val Arg Xaa Xaa
<210> 249 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 1-amino-l-cyclohexanecarboxylic acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-tetradecanoyl-lysine
<223> this sequence has an amidated c-terminus
<400> 249
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Glu Ala Ala Arg Glu Phe Ile Ala Trp Xaa Val Arg Xaa Xaa
<210> 250 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 1-amino-l-cyclohexanecarboxylic acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-hexadecanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 250
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Glu Ala Ala Arg Glu Phe Ile Ala Trp Xaa Val Arg Xaa Xaa
<210> 251 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 1-amino-l-cyclohexanecarboxylic acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-octanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 251
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Glu Xaa Ala Arg Glu Phe Ile Ala Trp Xaa Val Arg Xaa Xaa
<210> 252 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 1-amino-l-cyclohexanecarboxylic acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-tetradecanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 252
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Glu Xaa Ala Arg Glu Phe Ile Ala Trp Xaa Val Arg Xaa Xaa
<210> 253 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 1-amino-i-cyclohexanecarboxylic acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-hexadecanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 253
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Glu Xaa Ala Arg Glu Phe Ile Ala Trp Xaa Val Arg Xaa Xaa
<210> 254 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 1-amino-l-cyclohexanecarboxylic acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-octanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 254
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Glu Xaa Ala Arg Glu Phe Ile Xaa Trp Xaa Val Arg Xaa Xaa
<210> 255 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MOD_RES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 1-amino-l-cyclohexanecarboxylic acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-tetradecanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 255
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Glu Xaa Ala Arg Glu Phe Ile Xaa Trp Xaa Val Arg Xaa Xaa
<210> 256 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MOD_RES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> 1-amino-l-cyclohexanecarboxylic acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-hexadecanoyl-lysine
<223> this sequence has an amidated c-terminus <400> 256
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Glu Xaa Ala Arg Glu Phe Ile Xaa Trp Xaa Val Arg Xaa Xaa
<210> 257 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> N-alpha-(4-(2-hydroxyethyl)-1-piperazine-ethanesulfonyl)histidine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 257
Xaa Ala Glu Gly Thr Phe Thr Ser Asp Val. Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Xaa Arg
<210> 258 <211> 30
<212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> N-alpha-(4-(2-hydroxyethyl)-1-piperazine-ethanesulfonyl)histidine
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 258
Xaa Ala Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Xaa Arg
<210> 259 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> N-alpha-(4-(2-hydroxyethyl)-1-piperazine-ethanesulfonyl)histidine
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 259
Xaa Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Xaa Arg
<210> 260 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> N-alpha-(4-(2-hydroxyethyl)-1-piperazineacetyl)histidine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 260
Xaa Ala Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Xaa Arg
<210> 261 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> N-alpha-(4-(2-hydroxyethyl)-1-piperazineacetyl)histidine
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 261
Xaa Ala Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Xaa Arg
<210> 262 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> N-alpha-(4-(2-hydroxyethyl)-1-piperazineacetyl)histidine
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 262
Xaa Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Xaa Arg
<210> 263 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> N-alpha-tetradecanoyl-histidine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus
<400> 263
Xaa Ala Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Xaa Arg
<210> 264 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> N-alpha-tetradecanoyl-histidine
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 264
Xaa Ala Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Xaa Arg
<210> 265 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> N-alpha-tetradecanoyl-histidine
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 265
Xaa Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Xaa Arg
<210> 266 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> N-alpha-tetradecanoyl-histidine
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 266
Xaa Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Xaa Arg
<210> 267 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> N-alpha-tetradecanoyl-histidine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 267
Xaa Ala Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg
<210> 268 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> N-alpha-tetradecanoyl-histidine
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 268
Xaa Ala Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg
<210> 269 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> N-alpha-tetradecanoyl-histidine
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 269
Xaa Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg
<210> 270 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> N-alpha-tetradecanoyl-histidine
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 270
Xaa Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg
<210> 271 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> N-alpha-tetradecanoyl-histidine
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 271
Xaa Ala Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg
<210> 272 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> N-alpha-tetradecanoyl-histidine
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 272
Xaa Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg
<210> 273 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> N-alpha-tetradecanoyl-histidine
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> beta-alanine
<223> this sequence has an amidated c-terminus <400> 273
Xaa Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg
<210> 274 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-octanesulfonyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 274
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Xaa Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg
<210> 275 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-dodecanesulfonyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 275
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Xaa Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg
<210> 276 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-hexadecanesulfonyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus
<400> 276
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Xaa Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg
<210> 277 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-octanesulfonyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 277
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Xaa Xaa Arg
<210> 278 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-dodecanesulfonyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 278
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Xaa Xaa Arg
<210> 279 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-hexadecanesulfonyl-lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 279
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Xaa Xaa Arg
<210> 280 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-octanesulfonyl-lysine
<223> this sequence has an amidated c-terminus <400> 280
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Giu Phe Ile Ala Trp Leu Val Arg Xaa Xaa
<210> 281 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-hexadecanesulfonyl-lysine
<223> this sequence has an amidated c-terminus <400> 281
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Xaa
<210> 282 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> (1-(4-decylpiperazine))aspartic acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 282
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Xaa Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg
<210> 283 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> (1-(4-dodecylpiperazine))aspartic acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 283
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Xaa Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg
<210> 284 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> (1-(4-tetradecyl.piperazine))aspartic acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 284
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Xaa Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg
<210> 285 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> (1-(4-hexadecylpiperazine))aspartic acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 285
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Xaa Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg
<210> 286 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> (1-(4-decylpiperazine))aspartic acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 286
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Xaa Xaa Arg
<210> 287 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MOD_RES
<223> (1-(4-dodecylpiperazine))aspartic acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 287
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Xaa Xaa Arg
<210> 288 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> (1-(4-tetradecylpiperazine))aspartic acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 288
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Xaa Xaa Arg
<210> 289 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> (1-(4-hexadecylpiperazine))aspartic acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 289
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Xaa Xaa Arg
<210> 290 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> (1-(4-decylpiperazine))aspartic acid
<223> this sequence has an amidated c-terminus <400> 290
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Xaa
<210> 291 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> (1-(4-dodecylpiperazine))aspartic acid
<223> this sequence has an amidated c-terminus <400> 291
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Xaa
<210> 292 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> (1-(4-hexadecylpiperazine))aspartic acid
<223> this sequence has an amidated c-terminus
<400> 292
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Xaa
<210> 293 <211> 32 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> (1-(4-decylpiperazine))aspartic acid
<223> this sequence has an amidated c-terminus <400> 293
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg Gly Xaa
<210> 294 <211> 32 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> (1-(4-dodecylpiperazine))aspartic acid
<223> this sequence has an amidated c-terminus <400> 294
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg Gly Xaa
<210> 295 <211> 32 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> (1-(4-tetradecylpiperazine))aspartic acid
<223> this sequence has an amidated c-terminus <400> 295
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg Gly Xaa
<210> 296 <211> 32 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MOD RES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> (1-(4-hexadecylpiperazine))aspartic acid
<223> this sequence has an amidated c-terminus <400> 296
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg Gly Xaa
<210> 297 <211> 32 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> (1-(4-decylpiperazine))aspartic acid
<223> this sequence has an amidated c-terminus <400> 297
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg Xaa Xaa
<210> 298 <211> 32 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> (1-(4-dodecylpiperazine))aspartic acid
<223> this sequence has an amidated c-terminus <400> 298
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gin Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg Xaa Xaa
<210> 299 <211> 32 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> (1-(4-tetradecylpiperazine))aspartic acid
<223> this sequence has an amidated c-terminus <400> 299
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg Xaa Xaa
<210> 300 <211> 32 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> (1-(4-hexadecylpiperazine))aspartic acid
<223> this sequence has an amidated c-terminus <400> 300
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg Xaa Xaa
<210> 301 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> (1-(4-decylpiperazine))aspartic acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 301
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Xaa Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg
<210> 302 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> (1-(4-dodecylpiperazine))aspartic acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus
<400> 302
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Xaa Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg
<210> 303 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> (1-(4-tetradecylpiperazine))aspartic acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 303
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Xaa Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg
<210> 304 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> (1-(4-hexadecylpiperazine))aspartic acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 304
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Xaa Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg
<210> 305 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> (1-(4-decylpiperazine))aspartic acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 305
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Xaa Xaa Arg
<210> 306 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> (1-(4-dodecylpiperazine))aspartic acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 306
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Xaa Xaa Arg
<210> 307 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> (1-(4-tetradecylpiperazine))aspartic acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 307
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Xaa Xaa Arg
<210> 308 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> (1-(4-hexadecylpiperazine))aspartic acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 308
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Xaa Xaa Arg
<210> 309 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> (1-(4-decylpiperazine))aspartic acid
<223> this sequence has an amidated c-terminus <400> 309
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Xaa
<210> 310 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> (1-(4-dodecylpiperazine))aspartic acid
<223> this sequence has an amidated c-terminus <400> 310
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Xaa
<210> 311 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> (1-(4-tetradecylpiperazine))aspartic acid
<223> this sequence has an amidated c-terminus <400> 311
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Xaa
<210> 312 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> (1-(4-hexadecylpiperazine))aspartic acid
<223> this sequence has an amidated c-terminus <400> 312
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Xaa
<210> 313 <211> 32 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MOD_RES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> (1-(4-decyipiperazine))aspartic acid
<223> this sequence has an amidated c-terminus <400> 313
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg Gly Xaa
<210> 314 <211> 32 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> (1-(4-dodecylpiperazine))aspartic acid
<223> this sequence has an amidated c-terminus <400> 314
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg Gly Xaa
<210> 315 <211> 32 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> (1-(4-tetradecylpiperazine))aspartic acid
<223> this sequence has an amidated c-terminus <400> 315
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg Gly Xaa
<210> 316 <211> 32 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> (1-(4-hexadecylpiperazine))aspartic acid
<223> this sequence has an amidated c-terminus <400> 316
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg Gly Xaa
<210> 317 <211> 32 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> (1-(4-decylpiperazine))aspartic acid
<223> this sequence has an amidated c-terminus <400> 317
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg Xaa Xaa
<210> 318 <211> 32 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MOD_RES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> (1-(4-dodecylpiperazine))aspartic acid
<223> this sequence has an amidated c-terminus <400> 318
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg Xaa Xaa
<210> 319 <211> 32 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> (1-(4-tetradecylpiperazine))aspartic acid
<223> this sequence has an amidated c-terminus <400> 319
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg Xaa Xaa
<210> 320 <211> 32 <212> PRT
<213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> (1-(4-hexadecylpiperazine))aspartic acid
<223> this sequence has an amidated c-terminus <400> 320
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg Xaa Xaa
<210> 321 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MOD_RES
<223> (1-dodecylamino))glutamic acid
<223> this sequence has an amidated c-terminus <400> 321
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Xaa
<210> 322 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> (1-dodecylamino))glutamic acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 322
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Xaa Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg
<210> 323 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> (1-dodecylamino))glutamic acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 323
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Xaa Xaa Arg
<210> 324 <211> 32 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> (1-dodecylamino))glutamic acid
<223> this sequence has an amidated c-terminus <400> 324
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg Xaa Xaa
<210> 325 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-(2-(4-decyl-l-piperazine)-acetyl)lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 325
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Xaa Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg
<210> 326 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-(2-(4-dodecyl-l-piperazine)-acetyl)lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 326
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Xaa Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg
<210> 327 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-(2-(4-tetradecyl-l-piperazine)-acetyl)lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 327
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Xaa Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg
<210> 328 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-(2-4-hexadecyl-l-piperazine)-acetyl)lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 328
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Xaa Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg
<210> 329 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-(2-(4-decyl-i-piperazine)-acetyl)lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 329
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Xaa Xaa Arg
<210> 330 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MOD_RES
<223> N-epsilon-(2-(4-dodecyl-l-piperazine)-acetyl)lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 330
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Xaa Xaa Arg
<210> 331 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-(2-(4-tetradecyl-l-piperazine)-acetyl)lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 331
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Xaa Xaa Arg
<210> 332 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-(2-(4-hexadecyl-l-piperazine)-acetyl)lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 332
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Xaa Xaa Arg
<210> 333 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-(2-(4-decyl-l-piperazine)-acetyl)lysine
<223> this sequence has an amidated c-terminus <400> 333
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Xaa
<210> 334 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MOD_RES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-(2-(4-dodecyl-l-piperazine)-acetyl)lysine
<223> this sequence has an amidated c-terminus <400> 334
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Xaa
<210> 335 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-(2-(4-hexadecyl-l-piperazine)-acetyl)lysine
<223> this sequence has an amidated c-terminus
<400> 335
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Xaa
<210> 336 <211> 32 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-(2-(4-decyl-l-piperazine)-acetyl)lysine
<223> this sequence has an amidated c-terminus <400> 336
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg Gly Xaa
<210> 337 <211> 32 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-(2-(4-dodecyl-l-piperazine)-acetyl)lysine
<223> this sequence has an amidated c-terminus <400> 337
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg Gly Xaa
<210> 338 <211> 32 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-(2-(4-tetradecyl-i-piperazine)-acetyl)lysine
<223> this sequence has an amidated c-terminus <400> 338
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg Gly Xaa
<210> 339 <211> 32 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-(2-(4-hexadecyl-l-piperazine)-acetyl)lysine
<223> this sequence has an amidated c-terminus <400> 339
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg Gly Xaa
<210> 340 <211> 32 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-(2-(4-decyl-l-piperazine)-acetyl)lysine
<223> this sequence has an amidated c-terminus <400> 340
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg Xaa Xaa
<210> 341 <211> 32 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-(2-(4-dodecyl-l-piperazine)-acetyl)lysine
<223> this sequence has an amidated c-terminus <400> 341
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg Xaa Xaa
<210> 342 <211> 32 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-(2-(4-tetradecyl-l-piperazine)-acetyl)lysine
<223> this sequence has an amidated c-terminus <400> 342
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg Xaa Xaa
<210> 343 <211> 32 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MOD_RES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-(2-(4-hexadecyl-l-piperazine)-acetyl)lysine
<223> this sequence has an amidated c-terminus <400> 343
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg Xaa Xaa
<210> 344 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-(2-(4-decyl-l-piperazine)-acetyl)lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 344
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Xaa Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg
<210> 345 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-(2-(4-dodecyl-l-piperazine)-acetyl)lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus
<400> 345
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Xaa Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg
<210> 346 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-(2-(4-tetradecyl-l-piperazine)-acetyl)lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 346
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Xaa Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg
<210> 347 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-(2-(4-hexadecyl-l-piperazine)-acetyl)lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 347
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Xaa Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg
<210> 348 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-(2-(4-decyl-l-piperazine)-acetyl)lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 348
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Xaa Xaa Arg
<210> 349 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-(2-(4-dodecyl-l-piperazine)-acetyl)lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 349
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Xaa Xaa Arg
<210> 350 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-(2-(4-tetradecyl-l-piperazine)-acetyl)lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 350
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Xaa Xaa Arg
<210> 351 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-(2-(4-hexadecyl-l-piperazine)-acetyl)lysine
<221> MODRES
<223> alpha-aminoisobutyric acid
<223> this sequence has an amidated c-terminus <400> 351
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Xaa Xaa Arg
<210> 352 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-(2-(4-decyl-l-piperazine)-acetyl)lysine
<223> this sequence has an amidated c-terminus <400> 352
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Xaa
<210> 353 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-(2-(4-dodecyl-l-piperazine)-acetyl)lysine
<223> this sequence has an amidated c-terminus <400> 353
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Xaa
<210> 354 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-(2-(4-tetradecyl-l-piperazine)-acetyl)lysine
<223> this sequence has an amidated c-terminus <400> 354
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Xaa
<210> 355 <211> 30 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-(2-(4-hexadecyl-l-piperazine)-acetyl)lysine
<223> this sequence has an amidated c-terminus <400> 355
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gin Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Xaa
<210> 356 <211> 32 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MOD_RES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-(2-(4-decyl-l-piperazine)-acetyl)lysine
<223> this sequence has an amidated c-terminus <400> 356
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg Gly Xaa
<210> 357 <211> 32 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-(2-(4-dodecyl-l-piperazine)-acetyl)lysine
<223> this sequence has an amidated c-terminus <400> 357
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg Gly Xaa
<210> 358 <211> 32 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-(2-(4-tetradecyl-l-piperazine)-acetyl)lysine
<223> this sequence has an amidated c-terminus <400> 358
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg Gly Xaa
<210> 359 <211> 32 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-(2-(4-hexadecyl-l-piperazine)-acetyl)lysine
<223> this sequence has an amidated c-terminus <400> 359
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg Gly Xaa
<210> 360 <211> 32 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-(2-(4-decyl-i-piperazine)-acetyl)lysine
<223> this sequence has an amidated c-terminus <400> 360
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg Xaa Xaa
<210> 361 <211> 32 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MOD_RES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-(2-(4-dodecyl-l-piperazine)-acetyl)lysine
<223> this sequence has an amidated c-terminus <400> 361
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg Xaa Xaa
<210> 362 <211> 32 <212> PRT <213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-(2-(4-tetradecyl-l-piperazine)-acetyl)lysine
<223> this sequence has an amidated c-terminus <400> 362
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Giu Phe Ile Ala Trp Leu Val Arg Xaa Arg Xaa Xaa
<210> 363 <211> 32 <212> PRT
<213> Artificial Sequence
<223> Mutagen
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> alpha-aminoisobutyric acid
<221> MODRES
<223> N-epsilon-(2-(4-hexadecyl-l-piperazine)-acetyl)lysine
<223> this sequence has an amidated c-terminus <400> 363
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
Gln Ala Arg Arg Glu Phe Ile Ala Trp Leu Val Arg Xaa Arg Xaa Xaa