Structure-activity relationships of glucose-dependent insulinotropic polypeptide (GIP)

被引：18

作者：

Hinke, SA

Gelling, R

Manhart, S

Lynn, F

Pederson, RA

Kühn-Wache, K

Rosche, F

Demuth, HU

Coy, D

McIntosh, CHS

机构：

[1] Univ British Columbia, Dept Physiol, Vancouver, BC V6T 1Z3, Canada

[2] Probiodrug AG, Bioctr, D-06120 Halle An Der Saale, Germany

[3] Tulane Univ, Sch Med, New Orleans, LA 70112 USA

来源：

BIOLOGICAL CHEMISTRY | 2003年 / 384卷 / 03期

关键词：

Chinese hamster ovary cells; cyclic AMP; enteroinsular axis; gastric inhibitory polypeptide; incretin; radioligand binding competition;

D O I：

10.1515/BC.2003.046

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Six GIP(1-30NH2) analogs were synthesized with modifications (deprotonation, Nmethylation, reversed chirality, and substitution) at positions 1, 3, and 4 of the Nterminus, and additionally, a cyclized GIP derivative was synthesized. The relationship between altered structure to biological activity was assessed by measuring receptor binding affinity and ability to stimulate adenylyl cyclase in CHOK1 cells transfected with the wildtype GIP receptor (wtGIPR). These structureactivity relationship studies demonstrate the importance of the GIP Nterminus and highlight structural constraints that can be introduced in GIP analogs. These analogs may be useful starting points for design of peptides with enhanced in vivo bioactivity.

引用

收藏

页码：403 / 407

页数：5

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