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Pub. No.:    WO/2011/159882    International Application No.:    PCT/US2011/040677
Publication Date: 22.12.2011 International Filing Date: 16.06.2011
C07K 14/62 (2006.01), A61K 38/28 (2006.01)
Applicants: INDIANA UNIVERSITY RESEARCH AND TECHNOLOGY CORPORATION [US/US]; 351 West 10th Street Indianapolis, IN 46206 (US) (For All Designated States Except US).
DIMARCHI, Richard, D. [US/US]; (US) (For US Only).
HAN, Jie [CN/US]; (US) (For US Only).
MROZ, Piotr [PL/US]; (US) (For US Only)
Inventors: DIMARCHI, Richard, D.; (US).
HAN, Jie; (US).
MROZ, Piotr; (US)
Agent: ADDISON, Bradford, G.; Barnes & Thornburg LLP 11 South Meridian Street Indianapolis, IN 46204 (US)
Priority Data:
61/355,362 16.06.2010 US
Abstract: front page image
(EN)As disclosed herein a series of novel high potency insulin agonists have been designed, synthesized and characterized that relate to stabilization of the native alpha helical secondary structure of the insulin A and B chains. In accordance with one embodiment an insulin agonist analog is provided, comprising an A chain and a B chain sequence wherein the native alpha helical secondary structure has been stabilized in one or both of said A chain and B chain sequences by substitutions and/or additions of the native sequence with alpha, alpha disubstituted amino acids (e.g., amino isobutyric acid, Aib) or with amino acids that foster intramolecular interactions between amino acid side chains including the formation of lactams, lactones or salt bridges, or any combination thereof.
(FR)La présente invention concerne une série de nouveaux agonistes de l'insuline très puissants qui ont été conçus, synthétisés et caractérisés, et aident à la stabilisation de la structure alpha hélicoïdale secondaire native des chaînes A et B de l'insuline. Selon un mode de réalisation, l'invention concerne un analogue d'un agoniste de l'insuline, comprenant une séquence de chaîne A et de chaîne B, la structure alpha hélicoïdale secondaire native étant stabilisée dans l'une ou les deux séquences des chaînes A et B par le biais de substitutions et/ou d'additions dans la séquence native impliquant des acides aminés alpha, alpha disubstitués (par exemple, l'acide aminoisobutyrique, Aib) ou des acides aminés qui favorisent les interactions intramoléculaires entre les chaînes latérales des acides aminés, y compris la formation de lactames, de lactones ou de ponts salins, ou toute combinaison de ceux-ci.
Designated States: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW.
African Regional Intellectual Property Organization (BW, GH, GM, KE, LR, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, ZW)
Eurasian Patent Organization (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM)
European Patent Office (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR)
African Intellectual Property Organization (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG).
Publication Language: English (EN)
Filing Language: English (EN)