Structure-activity relationships of C-terminal tri- and tetrapeptide fragments that inhibit gastrin activity.
A series of tri- and tetrapeptide derivatives, analogues of the gastrin C-terminal region with no phenylalanine residue, were synthesized. These peptides were tested for their ability to inhibit gastrin-stimulated acid secretion in vivo as well as binding of [125I]-(Nle11)-HG-13 to gastric mucosal cell receptors in vitro. Most of the peptides tested exhibited gastrin antagonist activity in vivo and in vitro. Most active derivatives were 20-30 times more potent than the well-known gastrin antagonist derivatives proglumide and benzotript and had 20-200 times more binding affinity. The smallest fragment exhibiting antagonist activity was the tripeptide Boc-L-tryptophyl-L-methionyl-L-aspartic acid amide.
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D005744:Gastric Acid / Q000378:metabolism; D005755:Gastrins / Q000037:antagonists & inhibitors*; D009842:Oligopeptides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
D005755:Gastrins; D009842:Oligopeptides; D010446:Peptide Fragments