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 c...

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Bibliographic Details
Published in:Journal of medicinal chemistry 1985-03, Vol.28 (3), p.273-278
Main Authors: Martinez, Jean, Bali, Jean Pierre, Magous, Richard, Laur, Janine, Lignon, Marie Francoise, Briet, Christian, Nisato, Dino, Castro, Bertrand
Format: Article
Language:English
Subjects:
acids
Animals
Biological and medical sciences
Chemical Phenomena
Chemistry
Gastric Acid - metabolism
gastric mucosa
gastrin
Gastrins - antagonists & inhibitors
General pharmacology
Medical sciences
Oligopeptides - pharmacology
Peptide Fragments - pharmacology
peptide synthesis
Pharmacology. Drug treatments
Physicochemical properties. Structure-activity relationships
Rats
Structure-Activity Relationship
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Summary: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.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm00381a002