Conformational analysis of a peptide segment of gastrin in comparison with an antigastric benzothiazocine.

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Abstract
An examination of structural similarities between gastrins (3-5) and antigastric 5,1-benzothiazocines (2) suggested the presence of common functional groups and atoms, i.e., a benzene ring, a nonbasic nitrogen and a sulfur atom. A working hypothesis presuming these to be essential binding moieties is presented. A molecular mechanics calculation study of Ac-Trp-Met-NHMe (14) as a model peptide bearing the receptor binding sites was carried out in an attempt to find a stereochemical correlation with a representative 5,1-benzothiazocine, RS-2039 (1), a derivative of which had been structurally elucidated by X-ray crystallographic analysis. Several stable conformers of Ac-Trp-Met-NHMe were discovered to have a close approximation of the 3-dimensional array of binding sites to that of 1. It has thus been theoretically demonstrated that gastrins and 5,1-benzothiazocines could bind with an identical receptor.