Recherche dans les collections de brevets nationales et internationales
Une partie du contenu de cette demande n'est pas disponible pour le moment.
Si cette situation persiste, contactez-nous auObservations et contact
1. (WO2015176035) ANTAGONISTES PEPTIDIQUES DE L'INTÉGRINE Α4Β7 CONTENANT DES THIOÉTHERS
Note: Texte fondé sur des processus automatiques de reconnaissance optique de caractères. Seule la version PDF a une valeur juridique

CLAIMS

1. A peptide molecule comprising a structure of Formula (V):

Xaa -Xaa -Xaa -Xaa -Xaa -Xaa -Xaa -Xaa -Xaa -Xaa -Xaa -Xaa -Xaa -Xaa

(Formula (V))

or a pharmaceutically acceptable salt thereof, wherein the peptide comprises a thioether bond between Xaa4 and Xaa10, and wherein:

Xaa1 is absent, or Xaa1 is any amino acid;

Xaa2 is absent, or Xaa2 is any amino acid;

Xaa3 is absent, or Xaa3 is any amino acid;

Xaa4 is an amino acid, aliphatic acid, alicyclic acid, or modified 2-methyl aromatic acid having a side chain with one or two carbons, and capable of forming a thioether bond with Xaa10;

Xaa5 is selected from the group consisting of N(alpha)-Me-Arg, Arg, HomoArg, Dap, Dab, Arg-Me-sym, Arg-Me-asym, 4-Guan, Cit, Cav, N-Me-Lys, Phe(4-quanidino), Phe(4-carbamoyl amino), Phe(4-NH2), N-Me-HomoArg, Tyr, His, and suitable isostere

replacements;

Xaa6 is selected from the group consisting of Ser, Gly, Thr, He, and suitable isostere replacements;

Xaa7 is selected from the group consisting of Asp, N-Me-Asp, Asp(OMe), D-Asp, and suitable isostere replacements;

Xaa8 is selected from the group consisting of Thr, Gin, Ser, Asp, Pro, Gly, His, Ala, He, Phe, Lys, Arg, Asn, Glu, Val, Tyr, Trp, Leu, Met, HomoLeu, Nle, and N-Methyl amino acids including N-Me-Thr;

Xaa9 is selected from the group consisting of Gin, Asn, Asp, Pro, Gly, Ala, Phe, Leu, Glu, He, Val, HLeu, n-Butyl Ala, n-Pentyl Ala, n-Hexyl Ala, Nle, cyclobutyl-Ala, Cpa, Aoc, N-Me-Leu, and suitable isostere replacements;

Xaa10 is selected from the group consisting of Cys, N-Me-Cys, D-Cys, HCys, Pen, D-Pen, and Pen(=0);

Xaa11 is absent or is selected from the group consisting of: Trp, Phe, 2-Nal, 1-Nal, Tyr, His, Phe(4-F), Phe(4-CF3), Phe (4-CH3), Phe (4-tBu), Bip, Phe(4-COOH), Gly, 3,3-DiPhenylGly, 3,3 diPhenyl Ala, Tic, b-homo-Trp, D- 1-Nal, D-2-Nal, Phe(2,4-diCl), Phe(3,4-diCl), Phe(4-carbomyl), Phe(3-Carbomyl), Phe (2-carbomyl), Tyr(Me), HomoPhe, N-Me-Phe, N-Me-Tyr,

Ser, Sar, Dihydro Trp, He, Leu, Ser, Arg, Thr, Sar, and Ser, aromatic amino acids , substituted aromatic amino acids, Gly, Gin, Asn, Asp, Ala, He, Leu, Val, Met, Thr, Lys, Trp, Tyr, His, Glu, Ser, Arg, Pro, Phe, Sar, 1-Nal, 2-Nal, D-l-Nal, D-2-Nal, HPhe, D-Phe, D-Tyr, Phe(4-F), O-Me-Tyr, dihydro-Trp, Dap, Dab, Dab(Ac), Orn, D-Orn, N-Me-Orn, N-Me-Dap, D-Dap, D-Dab, Bip, Ala(3,3diphenyl), Biphenyl-Ala, aromatic ring substituted Phe, aromatic ring substituted Trp, aromatic ring substituted His, hetero aromatic amino acids, N-Me-Lys, N-Me-Lys(Ac), 4-Me-Phe, Phe(4tBu), Phe(4-OMe), Phe(4-COOH), Phe(2-carbomyl), Phe(3-carbomyl), Phe(CF3), Phe(2,4-diCl), Phe(3,4-diCl), Aic, N-Me-Tyr, N-Me-Phe, Tic,

Phe(4CF3), Bpa, Phe(3-Me), Phe(2-Me), Phe(2-CF3), β-Me-Phe, and corresponding D-amino acids and suitable isostere replacements;

Xaa12 is absent or selected from the group consisting of aromatic amino acids, substituted aromatic amino acids, Glu, D-Glu, HomoGlu, Beta-Homo-Glu, Asp, D-HomoGlu, Amide, Lys, COOH, CONH2, Gin, Pro, Gly, His, Ala, He, Phe, Arg, Leu, Val, Tyr, Trp, Met, Gla, Ser, Asn, D-Glu, β-HGlu, 2-Nal, 1-Nal, D-Asp, Bip, β-HPhe, β-Glu, D-Tyr, D-Phe, D-Lys, Dap, Dab, Orn, D-Orn, N-Me-Orn, N-Me-Dap, N-Me-Dab, N-Me Lys, D-Dap, D-Dab, D-His, F(4-COOH), Tic, D-Trp, D-Leu, D-Arg, D-Thr, N-Me-Glu, N-Me-Asp, alpha-H-Glu, isosteres, and corresponding D-amino acids;

Xaa13 is absent or any amino acid; and

Xaa14 is absent or any amino acid;

wherein if the peptide molecule is a peptide dimer or subunit thereof, then Xaa14 is absent or selected from the group consisting of: any amino acid with an amine side chain, Lys, D-Lys, N-Me-Lys, D-N-Me-Lys, Orn, N-Me-Orn, Dab, N-Me-Dab, Dap, N-Me-Dap, Homo-Lys, D-Dap, D-Dab, D-Orn, Gin, Pro, Gly, His, Ala, He, Phe, Lys, Arg, Leu, Val, Tyr, Trp, Met, Glu, Ser, Asn, Gla, Cys, HomoCys, COOH, CONH2, suitable isosteres, corresponding D-amino acids, and corresponding N-Methyl amino acids, and

wherein the peptide molecule comprises a thioether bond between Xaa4 and Xaa10.

2. The peptide molecule of claim 1, wherein

Xaa1 is absent or any amino acid;

Xaa2 is absent or any amino acid;

Xaa3 is absent or any amino acid;

Xaa4 is a 2-methyl-benzoyl moiety or a modified HomoSer, optionally Homo-Ser-Cl;

Xaa5 is selected from the group consisting of: N-Me-Arg, Arg, N-Me-Lys, Phe (4-quanidino), Phe(4-carbonylamino), Cit, Phe(4-NH2), N-Me-Homo-Arg, Homo-Arg, Tyr and His;

Xaa6 is Ser, Gly, Thr or He;

Xaa7 is Asp or D-Asp;

Xaa8 is selected from the group consisting of: Thr, Val, He, Leu, hLeu, Nle, and Val;

Xaa9 is selected from the group consisting of: Leu, Nle, Cpa, Cba, HomoLeu, Aoc, and N- Me-Leu;

Xaa10 is Pen, Cys, D-Cys or HomoCys; and

Xaa11 is absent or selected from the group consisting of: Trp, Phe, 2-Nal, 1-Nal, Tyr, His, Phe(4-F), Phe(4-CF3), Phe (4-CH3), Phe (4-tBu), Bip, Phe(4-COOH), Gly, 3,3-DiPhenylGly, 3,3 diPhenyl Ala, Tic, b-homo-Trp, D- 1-Nal, D-2-Nal, Phe(2,4-diCl), Phe(3,4-diCl), Phe(4-carbomyl), Phe(3-Carbomyl), Phe (2-carbomyl), Tyr(Me), HomoPhe, N-Me-Phe, N-Me-Tyr, Ser, Sar, Dihydro Trp, He, Leu, Arg, Thr, Sar, Bpa, Phe(3-Me), Phe(2-Me), Phe(2-CF3), β-Me-Phe, and Ser;

Xaa12 is absent or selected from the group consisting of: any aromatic amino acid, Glu, D-Glu, homoGlu, Asp, D-Asp, D-homoGlu, D-Asp, Gla, beta-homo-Glu, N-Me-Glu, N-Me-Asp, alpha-H-Glu, corresponding D-amino acid, and isosteres;

Xaa13 is absent or any amino acid; and

Xaa14 is any amino acid.

3. The peptide molecule of claim 1, wherein

Xaa1 is absent or any amino acid;

Xaa2 is absent or any amino acid;

Xaa3 is absent or any amino acid;

Xaa4 is a 2-methylbenzoyl moiety or a modified HomoSer, optionally Homo-Ser-Cl;

Xaa5 is N-Me-Arg;

Xaa6 is Ser, Gly, Thr, or He;

Xaa7 is Asp or D-Asp;

Xaa8 is selected from the group consisting of: Thr, Val, He, Leu, hLeu and Nle;

Xaa9 is selected from the group consisting of: Leu, Nle, Cpa, Cba, HomoLeu, Aoc, and N- Me-Leu;

Xaa10 is Pen, Cys, D-Cys or HomoCys;

Xaa11 is selected from the group consisting of: Trp, Phe, 2-Nal, 1-Nal, Tyr, His, Phe(4-F), Phe(4-CF3), Phe (4-CH3), Phe (4-tBu), Bip, Phe(4-COOH), Gly, 3,3-DiPhenylGly, 3,3 diPhenyl Ala, Tic, b-homo-Trp, D- 1-Nal, D-2-Nal, Phe(2,4-diCl), Phe(3,4-diCl), Pge(4-carbomyl), Phe(3 -Carbomyl), Tyr(Me), HomoPhe, N-Me-Phe, N-Me-Tyr, Ser, Sar, Dihydro Trp, lie, Leu, Ser, Arg, Thr, Sar, Bpa, Phe(3-Me), Phe(2-Me), Phe(2-CF3), β-Me-Phe, Ser and any substituted aromatic amono acid and corresponding D-amino acids;

Xaa12 is selected from the group consisting of: any aromatic amino acid, Glu, D-Glu, homoGlu, Asp, D-Asp, D-homoGlu, Gla, beta-homo-Glu, N-Me-Glu, N-Me-Asp, alpha-H-Glu , corresponding D-amino acid and isosteres;

Xaa13 is absent; and

Xaa14 is any amino acid.

4. The peptide molecule of claim 1, wherein Xaa1 is absent or any amino acid;

Xaa2 is absent or any amino acid;

Xaa3 is absent or any amino acid;

Xaa4 is a 2-methylbenzoyl moiety or a modified HomoSer, optionally Homo-Ser-Cl;

Xaa5 is N-Me-Arg;

Xaa6 is Ser, Gly, Thr, or He;

Xaa7 is Asp or D-Asp;

Xaa8 is selected from the group consisting of: Thr, Val, He, Leu, hLeu and Nle;

Xaa9 is selected from the group consisting of: Leu, Nle, Cpa, Cba, HomoLeu, Aoc, and N- Me-Leu;

Xaa10 is Pen, Cys, D-Cys or HomoCys;

Xaa11 is selected from the group consisting of: Trp, Phe, 2-Nal, 1-Nal, Tyr, His, Phe(4-F), Phe(4-CF3), Phe (4-CH3). Phe (4-tBu), Bip, Phe(4-COOH), Gly, 3,3-DiPhenylGly, 3,3 diPhenyl Ala, Tic, b-homo-Trp, D- 1-Nal, D-2-Nal, Phe(2,4-diCl), Phe(3,4-diCl), Pge(4-carbomyl), Phe(3-Carbomyl), Tyr(Me), HomoPhe, N-Me-Phe, N-Me-Tyr, Sar, Dihydro Trp, He, Leu, Ser, Arg, Thr, Sar, Bpa, Phe(3-Me), Phe(2-Me), Phe(2-CF3), β-Me-Phe, and Ser; Xaa12 is selected from the group consisting of: any aromatic amino acid, Glu, D-Glu, homoGlu, Asp, D-Asp, D-homoGlu, Gla, beta-homo-Glu, N-Me-Glu, N-Me-Asp, alpha-H-Glu, corresponding D-amino acid and isosteres;

Xaa13 is absent or any amino acid; and

Xaa is any amino acid.

5. The peptide molecule of claim 1, wherein:

Xaa1 is absent or any amino acid;

Xaa2 is absent or any amino acid;

Xaa3 is absent or any amino acid;

Xaa4 is a 2-methylbenzoyl moiety or a modified HomoSer, optionally Homo-Ser-Cl;

Xaa5 is N-Me-Arg;

Xaa6 is Ser;

Xaa7 is Asp or D-Asp;

Xaa8 is Thr or Val;

Xaa9 is selected from the group consisting of: Leu, Nle, Cpa, Cba, HomoLeu, Aoc, and N-Me-Leu;

Xaa10 is Pen, Cys, D-Cys or HomoCys;

Xaa11 is selected from the group consisting of: Trp, Phe, 2-Nal, 1-Nal, Tyr, His, Phe(4-F), Phe(4-CF3), Phe (4-CH3), Phe (4-tBu), Bip, Phe(4-COOH), Gly, 3,3-DiPhenylGly, 3,3 diPhenyl Ala, Tic, b-homo-Trp, D-l-Nal, D-2-Nal, Phe(2,4-diCl), Phe(3,4-diCl), Pge(4-carbomyl), Phe(3-Carbomyl), Tyr(Me), HomoPhe, N-Me-Phe, N-Me-Tyr, Ser, Sar, Dihydro Trp, lie, Leu, Ser, Arg, Thr, Sar, Bpa, Phe(3-Me), Phe(2-Me), Phe(2-CF3), β-Me-Phe, and Ser;

Xaa12 is absent or selected from the group consisting of: any aromatic amino acid, Glu, D-Glu, homoGlu, Asp, D-Asp, D-homoGlu, Gla, beta-homo-Glu, N-Me-Glu, N-Me-Asp, alpha-H-Glu, corresponding D-amino acid and isosteres;

Xaa13 is absent; and

Xaa14 is any amino acid..

6. The peptide molecule of claim 1, wherein:

Xaa1 is absent or any amino acid;

Xaa2 is absent or any amino acid;

Xaa3 is absent or any amino acid;

Xaa4 is a 2-methylbenzoyl moiety or a modified HomoSer, optionally Homo-Ser-Cl;

Xaa5 is N-Me-Arg;

Xaa6 is Ser;

Xaa7 is Asp or D-Asp;

Xaa8 is Thr or Val;

Xaa9 is selected from the group consisting of: Leu, Nle, Cpa, Cba, HomoLeu, Aoc, and N-Me-Leu;

Xaa10 is Pen, Cys, D-Cys or HomoCys;

Xaa11 is selected from the group consisting of: Trp, Phe, 2-Nal, 1-Nal, Tyr, His, Phe(4-F), Phe(4-CF3), Phe (4-CH3). Phe (4-tBu), Bip, Phe(4-COOH), Gly, 3,3-DiPhenylGly, 3,3 diPhenyl Ala, Tic, b-homo-Trp, D- 1-Nal, D-2-Nal, Phe(2,4-diCl), Phe(3,4-diCl), Pge(4-carbomyl), Phe(3-Carbomyl), Tyr(Me), HomoPhe, N-Me-Phe, N-Me-Tyr, Ser, Sar, Dihydro Trp, lie, Leu, Ser, Arg, Thr, Sar, Bpa, Phe(3-Me), Phe(2-Me), Phe(2-CF3), β-Me-Phe, and Ser;

Xaa12 is absent or selected from the group consisting of: any aromatic amino acid, Glu, D-Glu, beta-homo-Glu, N-Me-Glu, N-Me-Asp, alpha-H-Glu;

Xaa13 is absent; and,

Xaa14 is any amino acid.

7. The peptide molecule of claim 1, wherein:

Xaa1 is absent or any amino acid;

Xaa2 is absent or any amino acid;

Xaa3 is absent or any amino acid;

Xaa4 is a 2-methylbenzoyl moiety or a modified HomoSer, optionally Homo-Ser-Cl;

Xaa5 is N-Me-Arg;

Xaa6 is Ser;

Xaa7 is Asp or D-Asp;

Xaa8 is Thr or Val;

Xaa9 is Leu;

Xaa10 is Pen, Cys, D-Cys or HomoCys;

Xaa11 is selected from the group consisting of: Trp, Phe, 2-Nal, 1-Nal, Tyr, His, Phe(4-F), Phe(4-CF3), Phe (4-CH3). Phe (4-tBu), Bip, Phe(4-COOH), Gly, 3,3-DiPhenylGly, 3,3 diPhenyl Ala, Tic, b-homo-Trp, D- 1-Nal, D-2-Nal, Phe(2,4-diCl), Phe(3,4-diCl), Pge(4-carbomyl), Phe(3-Carbomyl), Tyr(Me), HomoPhe, N-Me-Phe, N-Me-Tyr, Ser, Sar, Dihydro

Trp, lie, Leu, Ser, Arg, Thr, Sar, Bpa, Phe(3-Me), Phe(2-Me), Phe(2-CF3), β-Me-Phe, and Ser;

Xaa12 is selected from the group consisting of: any aromatic amino acid, Glu, D-Glu, beta-homo-Glu, N-Me-Glu, N-Me-Asp, alpha-H-Glu, corresponding D-amino acid and isosteres; Xaa13 is absent; and

Xaa14 is any amino acid.

8. The peptide molecule of claim 1, wherein:

Xaa1 is absent or any amino acid;

Xaa2 is absent or any amino acid;

Xaa3 is absent or any amino acid;

Xaa4 is a 2-methylbenzoyl moiety or a modified HomoSer, optionally Homo-Ser-Cl;

Xaa5 is N-Me-Arg;

Xaa6 is Ser;

Xaa7 is Asp or D-Asp;

Xaa8 is Thr or Val;

Xaa9 is Leu;

Xaa10 is Pen, Cys, D-Cys or HomoCys;

Xaa11 is selected from the group consisting of: Trp, Phe, 2-Nal, 1-Nal, Tyr, His, Phe(4-F), Phe(4-CF3), Phe (4-CH3). Phe (4-tBu), Bip, Phe(4-COOH), Gly, 3,3-DiPhenylGly, 3,3 diPhenyl Ala, Tic, b-homo-Trp, D-l-Nal, D-2-Nal, Phe(2,4-diCl), Phe(3,4-diCl), Pge(4-carbomyl), Phe(3-Carbomyl), Tyr(Me), HomoPhe, N-Me-Phe, N-Me-Tyr, Ser, Sar, Dihydro Trp, lie, Leu, Ser, Arg, Thr, Sar, Bpa, Phe(3-Me), Phe(2-Me), Phe(2-CF3), β-Me-Phe, and Ser;

Xaa12 is selected from the group consisting of: any aromatic amino acid, Glu, D-Glu, N-Me-Glu, N-Me- Asp, alpha-H-Glu, and beta-homo-Glu;

Xaa13 is absent; and

Xaa14 is any amino acid.

9. The peptide molecule of claim 1, wherein:

Xaa1 is absent or any amino acid;

Xaa2 is absent or any amino acid;

Xaa3 is absent or any amino acid;

Xaa4 is a 2-methylbenzoyl moiety or a modified HomoSer, optionally Homo-Ser-Cl;

Xaa5 is N-Me-Arg;

Xaa6 is Ser;

Xaa7 is Asp;

Xaa8 is Thr or Val;

Xaa9 is Leu;

Xaa10 is Pen, Cys, D-Cys or HomoCys;

Xaa11 is selected from the group consisting of: Trp, Phe, 2-Nal, 1-Nal, Tyr, His, Phe(4-F), Phe(4-CF3), Phe (4-CH3). Phe (4-tBu), Bip, Phe(4-COOH), Gly, 3,3-DiPhenylGly, 3,3 diPhenyl Ala, Tic, b-homo-Trp, D- 1-Nal, D-2-Nal, Phe(2,4-diCl), Phe(3,4-diCl), Pge(4-carbomyl), Phe(3-Carbomyl), Tyr(Me), HomoPhe, N-Me-Phe, N-Me-Tyr, Ser, Sar, Dihydro Trp, lie, Leu, Ser, Arg, Thr, Sar, Bpa, Phe(3-Me), Phe(2-Me), Phe(2-CF3), β-Me-Phe, and Ser;

Xaa12 is selected from the group consisting of: any aromatic amino acid, Glu, D-Glu, N-Me-Glu, N-Me- Asp, alpha-H-Glu, and beta-homo-Glu;

Xaa13 is absent; and

Xaa14 is any amino acid.

10. The peptide molecule of claim 1, wherein:

Xaa1 is absent or any amino acid;

Xaa2 is absent or any amino acid;

Xaa3 is absent or any amino acid;

Xaa4 is a 2-methylbenzoyl moiety or a modified HomoSer, optionally Homo-Ser-Cl;

Xaa5 is N-Me-Arg;

Xaa6 is Ser;

Xaa7 is Asp or D-Asp;

Xaa8 is Thr or Val;

Xaa9 is Leu;

Xaa10 is Pen, Cys, D-Cys or HomoCys;

Xaa11 is selected from the group consisting of: Trp, Phe, 2-Nal, 1-Nal, Tyr, His, Phe(4-F),

Phe(4-CF3), Phe (4-CH3). Phe (4-tBu), Bip, Phe(4-COOH), Gly, 3,3-DiPhenylGly, 3,3

diPhenyl Ala, Tic, b-homo-Trp, D-l-Nal, D-2-Nal, Phe(2,4-diCl), Phe(3,4-diCl), Pge(4-carbomyl), Phe(3 -Carbomyl), Tyr(Me), Bpa, Phe(3-Me), Phe(2-Me), Phe(2-CF3), β-Me-Phe, and HomoPhe;

Xaa12 is selected from the group consisting of: any aromatic amino acid, Glu, D-Glu, N-Me-Glu, N-Me- Asp, alpha-H-Glu, and beta-homo-Glu;

Xaa13 is absent; and

Xaa14 is any amino acid.

11. The peptide molecule of any one of claims 1-10, wherein Xaa1, Xaa2 and Xaa3 are absent.

12. The peptide molecule of any one of claims 1-11, wherein Xaa4 is a 2-methylbenzoyl moiety.

13. The peptide molecule of any one of claims 1-12, wherein Xaa5 is 2-Me-Arg.

14. The peptide molecule of any one of claims 1-13, wherein Xaa14 is selected from the group consisting of: Lys, D-Lys, N-Me-Lys, D-N-Me-Lys, Orn, Dab, Dap, Homo-Lys, D-Dap, D-Dab, Cys, HomoCys, Pen, or D-Orn.

15. The peptide molecule of any one of claims 1-14, wherein Xaa4 is a 2-methyl benzoyl moiety that forms a thioether bond with Xaa10, Xaa5 is N-Me-Arg, Xaa6 is Ser, Xaa7 is Asp, Xaa8 is Thr, Xaa9 is Leu, and Xaa10 is Pen, Cys, D-Cys or HomoCys.

16. The peptide molecule of claim 15, wherein Xaa10 is Pen or Cys.

17. The peptide molecule of any one of claims 1-15, wherein Xaa14 is selected from the group consisting of: D-Lys, N-Me-Lys, and D-N-Me-Lys.

18. The peptide molecule of any one of claims 1-17, comprising N(alpha)methylation of at least one position selected from the group consisting of Xaa3, Xaa5, Xaa7-Xaa9, and Xaa11- Xaa 13

19. The peptide molecule of any one of claims 1-18, comprising acylation for at least one position selected from the group consisting of Xaax-Xaa3 and Xaau-Xaa14.

20. A peptide molecule comprising a structure of Formula (VI):

Xaa -Xaa -Xaa -Xaa -Xaa -Xaa -Xaa -Xaa -Xaa -Xaa -Xaa

(Formula VI)

or a pharmaceutically acceptable salt thereof, wherein

Xaa1 is a 2-Me-benzoyl group capable of forming a thioether bond with Xaa7;

Xaa2 is selected from the group consisting of N(alpha)-Me-Arg, Arg, HArg, Dap, Dab, Arg- Me-sym, Arg-Me-asym, 4-Guan, Cit, Cav, and suitable isostere replacements;

Xaa3 is selected from the group consisting of Ser, Gly, and suitable isostere replacements;

Xaa4 is selected from the group consisting of Asp, N-Me-Asp, Asp(OMe), D-Asp, and a suitable isostere replacements;

Xaa5 is selected from the group consisting of Thr, Gin, Ser, Asp, Pro, Gly, His, Ala, He, Phe, Lys, Arg, Asn, Glu, Val, Tyr, Trp, Leu, Met, and N-Methyl amino acids including N-Me-Thr, and suitable isostere replacements;

Xaa6 is selected from the group consisting of Gin, Asn, Asp, Pro, Gly, Ala, Phe, Leu, Glu, He, Val, HLeu, n-Butyl Ala, n-Pentyl Ala, n-Hexyl Ala, Nle, cyclobutyl-Ala, N-Me-Leu, and suitable isostere replacements;

Xaa7 is selected from the group consisting of Cys, N-Me-Cys, D-Cys, HCys, Pen, and D-Pen; Xaa8 is selected from the group consisting of absent, Gly, Gin, Asn, Asp, Ala, He, Leu, Val, Met, Thr, Lys, Trp, Tyr, His, Glu, Ser, Arg, Pro, Phe, Sar, 1-Nal, 2-Nal, HPhe, Phe(4-F), O-Me-Tyr, dihydro-Trp, Dap, Dab, Dab(Ac), Orn, D-Orn, N-Me-Orn, N-Me-Dap, D-Dap, D-Dab, Bip, Ala(3,3diphenyl), Biphenyl-Ala, aromatic ring substituted Phe, aromatic ring substituted Trp, aromatic ring substituted His, hetero aromatic amino acids, N-Me-Lys, N-Me-Lys(Ac), Bpa, Phe(3-Me), Phe(2-Me), Phe(2-CF3), β-Me-Phe, 4-Me-Phe, and corresponding D-amino acids and suitable isostere replacements;

Xaa9 is selected from the group consisting of absent, Glu, Amide, Lys, COOH, CONH2, Gin, Pro, Gly, His, Ala, He, Phe, Lys, Arg, Leu, Val, Tyr, Trp, Met, Gla, Ser, Asn, D-Glu, β-HGlu, 2-Nal, 1-Nal, D-Asp, Bip, β-HPhe, β-Glu, D-Tyr, D-Lys, Dap, Dab, Orn, D-Orn, N-Me-Orn,

N-Me-Dap, N-Me-Dab, N-Me Lys, D-Dap, D-Dab, Glu, N-Me-Asp, alpha-H-Glu, suitable isosteres, and corresponding D-amino acids;

Xaa10 is selected from the group consisting of absent, Gin, Pro, Gly, His, Ala, He, Phe, Lys, Arg, Leu, Val, Tyr, Trp, Met, Glu, Ser, Asn, Gla, Dap, Dab, Om, D-Om, D-Lys, N-Me-Om, N-Me-Dap, N-Me-Dab, N-Me-Lys, D-Dap, D-Dab, COOH, CONH2, suitable isosteres, and corresponding D-amino acids; and

Xaa11 is selected from the group consisting of absent, Gin, Pro, Gly, His, Ala, He, Phe, Lys, Arg, Leu, Val, Tyr, Trp, Met, Glu, Ser, Asn, Gla, Dap, Dab, Om, D-Om, D-Lys, N-Me-Om, N-Me-Dap, N-Me-Dab, N-Me-Lys, D-Dap, D-Dab, COOH, CONH2, suitable isosteres, and corresponding D-amino acids, wherein the peptide further comprises a thioether bond between Xaa1 and Xaa7,

wherein the peptide further comprises a thioether bond between Xaa1 and Xaa7.

21. The peptide molecule of claim 20, wherein Xaa4 is a 2-methyl benzoyl moiety that forms a thioether bond with Xaa10, Xaa5 is N-Me- Arg, Xaa6 is Ser, Xaa7 is Asp, Xaa8 is Thr, Xaa9 is Leu, and Xaa10 is Pen, Cys, D-Cys or HomoCys.

22. The peptide molecule of claim 21, wherein Xaa10 is Pen or Cys

23. The peptide molecule of any one of claims 1-22, further comprising a terminal modifying group selected from the group consisting of DIG, PEG4, PEG13, PEG25, PEG IK, PEG2K, PEG4K, PEG5K, Polyethylene glycol having molecular weight from 400Da to 40,000Da, IDA, Ac-ID A, ADA, Glutaric acid, Isophthalic acid, 1,3-phenylenediacetic acid, 1,4-phenylenediacetic acid, 1 ,2-phenylenediacetic acid, AADA, suitable aliphatic acids, suitable aromatic acids, and heteroaromatic acids.

24. The peptide molecule of any one of claims 1-23, wherein the C-terminus of the peptide molecule further comprises a modifying group.

25. The peptide molecule of any one of claims 1-24, wherein the peptide molecule is a monomer.

26. The peptide molecule of any one of claims 1-24, wherein the peptide molecule is a dimer.

27. The peptide molecule of claim 26, comprsing two peptide molecules dimerized by a linker.

28. The peptide molecule of claim 27, where in the linker is selected from the group consisting of: DIG, PEG4, PEG4-biotin, PEG13, PEG25, PEG IK, PEG2K, PEG3.4K, PEG4K, PEG5K, IDA, ADA, Boc-IDA, Glutaric acid, Isophthalic acid, 1,3-phenylenediacetic acid, 1 ,4-phenylenediacetic acid, 1 ,2-phenylenediacetic acid, Triazine, Boc-Triazine, IDA-biotin, PEG4-Biotin, AADA, suitable aliphatics, aromatics,

heteroaromatics, and polyethylene glycol based linkers having a molecular weight from approximately 400Da to approximately 40,000Da.

29. A peptide molecule of claim 27 or claim 28, wherein the two peptide molecules are dimerized via their C-termini.

30 A pharmaceutical composition comprising a peptide molecule of any one of claims 1-29 and a pharmaceutically acceptable carrier, diluent or excipient.

31. The pharmaceutical composition of claim 30, wherein the pharmaceutical composition is formulated for oral delivery.

32. The pharmaceutical composition of claim 30 or claim 31, further comprising an enteric coating.

33. The pharmaceutical composition of claim 32, wherein the enteric coating releases the pharmaceutical composition within a subject's lower gastrointestinal system.

34. A method for treating or preventing a disease or condition that is associated with a biological function of integrin α4β7, the method comprising providing to a subject in need thereof an effective amount of the peptide molecule of any one of claims 1-29 or the pharmaceutical composition of any one of claims 30-33.

35. The method of claim 34, wherein the disease or condition is selected from the group consisting of Inflammatory Bowel Disease (IBD), adult IBD, pediatric IBD, adolescent IBD, ulcerative colitis, Crohn's disease, Celiac disease {nontropical Sprue) , enteropathy associated with seronegative arthropathies, microscopic colitis, collagenous colitis, eosinophilic gastroenteritis, radiotherapy, chemotherapy, pouchitis resulting after proctocolectomy and ileoanal anastomosis, gastrointestinal cancer, pancreatitis, insulin-dependent diabetes mellitus, mastitis, cholecystitis, cholangitis, pericholangitis, chronic bronchitis, chronic sinusitis, asthma, primary sclerosing cholangitis, human immunodeficiency virus (HIV) infection in the GI tract, eosinophilic asthma, eosinophilic esophagitis, gastritis, colitis, microscopic colitis and graft versus host disease (GVDH).

36. The method of claim 34, wherein the disease or condition is an inflammatory bowel disease.

37. The method of claim 36, wherein the inflammatory bowel disease is ulcerative colitis.

38. The method of claim 36, wherein the inflammatory bowel disease is Crohn's disease.

39. The method of any one of claims 34-38, wherein the peptide molecule inhibits binding of α4β7 to MAdCAM.

40. The method of any one of claims 34-39, wherein the peptide molecule or the

pharmaceutical composition is provided to the subject in need thereof at an interval sufficient to ameliorate the condition.

41. The method of claim 40, wherein the interval is selected from the group consisting of around the clock, hourly, every four hours, once daily, twice daily, three times daily, four times daily, every other day, weekly, bi-weekly, and monthly.

42. The method of any one of claims 34-41, wherein the peptide molecule or pharmaceutical composition is provided as an initial does followed by one or more subsequent doses, and the minimum interval between any two doses is a period of less than 1 day, and wherein each of the doses comprises an effective amount of the peptide molecule.

43. The method of any one of claims 34-42, wherein the effective amount of the peptide molecule or the pharmaceutical composition is sufficient to achieve at least one of the following: a) about 50% or greater saturation of MAdCAM binding sites on α4β7 integrin molecules; b) about 50%> or greater inhibition of α4β7 integrin expression on the cell surface; and c) about 50% or greater saturation of MAdCAM binding sites on α4β7 molecules and about 50% or greater inhibition of α4β7 integrin expression on the cell surface, wherein i) the saturation is maintained for a period consistent with a dosing frequency of no more than twice daily; ii) the inhibition is maintained for a period consistent with a dosing frequency of no more than twice daily; or iii) the saturation and the inhibition are each maintained for a period consistent with a dosing frequency of no more than twice daily.

44. The method of any one of claims 34-43, wherein the peptide molecule is administered orally.

45. The method of any one of claims 34-43, wherein the peptide molecule is administered parenterally.

46. The method of any one of claims 34-43, wherein the peptide molecule is administered topically.