title: Structure-activity relationships of glucose-dependent insulinotropic polypeptide (GIP).
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.
authors.affiliation: Department of Physiology, University of British Columbia, Vancouver, B.C., Canada V6T 1Z3.
authors.forename: Simon A
authors.initials: SA
authors.lastname: Hinke
authors.forename: Rick
authors.initials: R
authors.lastname: Gelling
authors.forename: Susanne
authors.initials: S
authors.lastname: Manhart
authors.forename: Francis
authors.initials: F
authors.lastname: Lynn
authors.forename: Raymond A
authors.initials: RA
authors.lastname: Pederson
authors.forename: Kerstin
authors.initials: K
authors.lastname: Kühn-Wache
authors.forename: Fred
authors.initials: F
authors.lastname: Rosche
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Demuth
authors.forename: David
authors.initials: D
authors.lastname: Coy
authors.forename: Christopher H S
authors.initials: CH
authors.lastname: McIntosh
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D016466:CHO Cells; D006224:Cricetinae; D000242:Cyclic AMP / Q000096:biosynthesis; D004789:Enzyme Activation; D005749:Gastric Inhibitory Polypeptide / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D007328:Insulin; D010446:Peptide Fragments; D005749:Gastric Inhibitory Polypeptide; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D005947:Glucose