Synthesis and biological activity of new peptide segments of gastrin exhibiting gastrin antagonist property

Abstract

A series of C-terminal peptide segments of gastrin, i.e., (tert-butyloxycarbonyl)-L-tryptophyl-L-methionyl-L-aspartic acid amide, (tert-butyloxycarbonyl)-glycyl-L-tryptophyl-L-methionyl-L-aspartic acid amide, (tert-butyloxycarbonyl)-L-tyrosyl-glycyl-L-tryptophyl-L-methionyl-L-aspartic acid amide and (benzyloxycarbonyl)-L-glutamyl-L-alanyl-L-tyrosyl-glycyl-L-tryptophyl-L-methionyl-L-aspartic acid amide, were prepared and competitively inhibited the binding of labeled human gastrin to its receptors in an isolated gastric mucosal cell preparation and antagonized the action of gastrin on gastric acid secretion (ED50 from 1.5-7 mg/kg) in vivo in the reperfused rat stomach; this was determined according to the method of Ghosh and Schild. The C-terminal phenylalanine residue, which is of primary importance for intrinsic biological gastrin-like activity, is evidently not essential for binding to gastrin receptors.