Abstract
Conformational analysis of the minimum active unit of gastrin, tetragastrin (Trp-Met-Asp-Phe-NH2), led to the formulation of common hypothetical receptor binding moieties with 5, 1-benzothiazocines, these moieties being a benzene ring, a nonbasic nitrogen and a hydrophobic group. A molecular mechanics calculation study of tetragastrin was carried out in an attempt to find a stereochemical correlation with a representative 5, 1-benzothiazocine, RS-2039, which had been structurally elucidated by X-ray crystallographic analysis. Several stable conformers of tetragastrin were discovered to have a close approximation of the 3-dimensional array of receptor binding moieties to that of RS-2039. It has thus been theoretically demonstrated that gastrins and 5, 1-benzothiazocines could bind with an identical receptor.
