Contribution of site-specific PEGylation to the dipeptidyl peptidase IV stability of glucose-dependent insulinotropic polypeptide

被引：28

作者：

Salhanick, AI

Clairmont, KB

Buckholz, TM

Pellegrino, CM

Ha, S

Lumb, KJ

机构：

[1] Bayer Pharmaceut Corp, Dept Res Technol, West Haven, CT 06516 USA

[2] Bayer Pharmaceut Corp, Dept Metab Disorders Res, West Haven, CT 06516 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 18期

关键词：

GIP; PEGylation; DPPIV;

D O I：

10.1016/j.bmcl.2005.06.002

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The effects of PEGylation of glucose-dependent insulinotropic polypeptide (GIP) on potency and dipeptidyl peptidase IV (DPPIV) stability are reported. N-terminal modification of GIP(1-30) with 40 kDa polyethylene glycol (PEG) abrogates functional activity. In contrast, C-terminal PEGylation of GIP(1-30) maintains full agonism and reasonable potency at the GIP receptor and confers a high level of DPPIV resistance. Moreover, the dual modification of N-terminal palmitoylation and C-terminal PEGylation results in a full agonist of comparable potency to native GIP that is stable to DPPIV cleavage. The results provide the basis for the development of long acting, PEGylated GIP, GIP variants, or GIP-based hybrid peptide therapeutics. (c) 2005 Elsevier Ltd. All rights reserved.

引用

收藏

页码：4114 / 4117

页数：4

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