SONG, DAE HAE,LIM, CHANG KI,SONG, TAE HUN,KIM, YOUNG HOON,KWON, SE CHANG,LEE, GWAN SUN,JUNG, SUNG YOUB,CHOI, IN YOUNG
申请号：
NZ57781208
公开号：
NZ577812A
申请日:
2008.01.04
申请国别(地区):
NZ
年份:
2012
代理人:
摘要：
Disclosed is an insulinotropic peptide conjugate, comprising: an insulinotropic peptide and an immunoglobulin Fc region, which are linked by a non-peptidyl polymer, wherein the insulinotropic peptide is selected from the group consisting of: exendin-4, an exendin-4 derivative prepared by deleting N-terminal amine group, an exendin-4 derivative prepared by substituting N-terminal amine group with hydroxyl group, an exendin-4 derivative prepared by modifying N-terminal amine group with dimethyl group, an exendin-4 derivative prepared by deleting á-carbon of histidine, the first amino acid of exendin-4, an exendin-4 derivative prepared by substituting 12th amino acid(lysine) for serine, and an exendin-4 derivative prepared by substituting 12th amino acid(lysine) with arginine, wherein the nonpeptidyl polymer is selected from the group consisting of: polyethylene glycol, polypropylene glycol, copolymers of ethylene glycol and propylene glycol, polyoxyethylated polyols, polyvinyl alcohol, polysaccharides, dextran, polyvinyl ethyl ether, biodegradable polymers, lipid polymers, chitins, hyaluronic acid, and combinations thereof, and wherein one end of the non-peptidyl polymer is linked to an amino acid residue other than the N-terminus of the insulinotropic peptide. Further disclosed is an insulinotropic peptide conjugate represented by the following Chemical Formula 1: R1-X-Y-Z-R2 wherein, R1 is selected from the group consisting of histidine, des-aminohistidyl group, N-dimethyl-histidyl group, beta-hydroxy imidazopropyl group and 4-imidazoacetyl group； R2 is selected from the group consisting of -NH2, -OH and -Lys； X is selected from the group consisting of GIy-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-R3-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-R4-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser, GIy-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-R3-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-R4-Asn-Gly-Gly, and Ser-Asp-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-R3-Gln-Me
