Structure-Activity Relationships of Glucose-Dependent Insulinotropic Polypeptide (GIP)
- 14 January 2003
- journal article
- Published by Walter de Gruyter GmbH in Biological Chemistry
- Vol. 384 (3) , 403-7
- https://doi.org/10.1515/bc.2003.046
Abstract
Six GIP(1-NH2) analogs were synthesized with modifications (de-protonation, N-methylation, reversed chirality, and substitution) at positions 1, 3, and 4 of the N-terminus, 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 CHO-K1 cells transfected with the wild-type GIP receptor (wtGIPR). These structure-activity relationship studies demonstrate the importance of the GIP N-terminus 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.Keywords
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