Structure-Activity Relationships of Glucose-Dependent Insulinotropic Polypeptide (GIP)

• Published in: Biological chemistry Vol. 384; no. 3; pp. 403 - 407
• Main Authors: Hinke, S.A., Gelling, R., Manhart, S., Lynn, F., Pederson, R.A., Kühn-Wache, K., Rosche, F., Demuth, H.-U., Coy, D., McIntosh, C.H.S.
• Format: Journal Article
• Language: English
• Published: Germany Walter de Gruyter 01.03.2003
• Subjects: Adenylyl Cyclases - metabolism; Animals; Binding, Competitive; CHO Cells; Cricetinae; Cyclic AMP - biosynthesis; Enzyme Activation; Gastric Inhibitory Polypeptide - chemistry; Gastric Inhibitory Polypeptide - metabolism; Gastric Inhibitory Polypeptide - pharmacology; Glucose - metabolism; Insulin - metabolism; Insulin Secretion; Peptide Fragments - chemistry; Peptide Fragments - metabolism; Peptide Fragments - pharmacology; Structure-Activity Relationship
• ISSN: 1431-6730
• DOI: 10.1515/BC.2003.046

Six GIP1-30NH2 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 structureactivity 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.