CORRELATION-ANALYSIS AND MOLECULAR MODELING OF CHOLECYSTOKININ INHIBITORS

Quantitative structure‐activity relationships for a series of N‐(R‐benzoyl)‐glutamic acid α‐alkylamides as cholecystokinin inhibitors have been elucidated. The relationships clearly define a hydrophobic binding pocket on the receptor which accomodates the alkylamides. A second hydrophobic binding region appears to interact with the benzoyl substituents. Computer graphic modeling suggests that these hydrophobic binding regions correspond to Met31 and Trp30 amino acid residues of the peptide agonist. A comparative analysis of potential carboxylate binding via GRID provides a quantitative assessment of similarities and differences between the glutamate inhibitors and the peptide agonist. Copyright © 1990 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim