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Title: Carbobenzoxy amino acids: Structural requirements for cholecystokinin receptor antagonist activity

The authors used dispersed acini prepared from guinea pig pancreas to examine 28 carbobenzoxy (CBZ) amino acids for their abilities to function as cholecystokinin receptor antagonists. All amino acid derivatives tested, except for CBZ-alanine, CBZ-glycine, and N alpha-CBZ- lysine, were able to inhibit the stimulation of amylase secretion caused by the C-terminal octapeptide of cholecystokinin. In general, there was a good correlation between the ability of a carbobenzoxy amino acid to inhibit stimulated amylase secretion and the ability of the amino acid derivative to inhibit binding of /sup 125/I-cholecystokinin. The inhibition of cholecystokinin-stimulated amylase secretion was competitive, fully reversible, and specific for those secretagogues that interact with the cholecystokinin receptor. The potencies with which the various carbobenzoxy amino acids inhibited the action of cholecystokinin varied 100-fold and CBZ-cystine was the most potent cholecystokinin receptor antagonist. This variation in potency was primarily but not exclusively a function of the hydrophobicity of the amino acid side chain.
Authors:
; ; ;
Publication Date:
OSTI Identifier:
5483935
Resource Type:
Journal Article
Resource Relation:
Journal Name: Am. J. Physiol.; (United States); Journal Volume: 248
Research Org:
National Institute of Arthritis, Bethesda, MD
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; AMINO ACIDS; BIOCHEMICAL REACTION KINETICS; AMYLASE; ENZYME ACTIVITY; HORMONES; RECEPTORS; ALANINES; CYSTINE; GLYCINE; GUINEA PIGS; HORMONE ANTAGONISTS; LYSINE; POLYPEPTIDES; STRUCTURE-ACTIVITY RELATIONSHIPS; ANIMALS; CARBOXYLIC ACIDS; DISULFIDES; DRUGS; ENZYMES; GLYCOSYL HYDROLASES; HYDROLASES; KINETICS; MAMMALS; O-GLYCOSYL HYDROLASES; ORGANIC ACIDS; ORGANIC COMPOUNDS; ORGANIC SULFUR COMPOUNDS; PEPTIDES; PROTEINS; REACTION KINETICS; RODENTS; VERTEBRATES 550201* -- Biochemistry-- Tracer Techniques