Marc Rodriguez, N. Bernad, M. Galas
Apr 1, 1991
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Journal
European Journal of Medicinal Chemistry
Abstract
Abstract Acetyl derivatives of ethyl esters of 3-(1-naphthyl)- d,l -alanine and 3-(2-naphthyl)- d,l -alanine were synthesized through a malonic condensation. Resolution of these derivatives by subtilisin Carlsberg followed by acid hydrolysis afforded the 2 optical isomers of 3-(1-naphthyl)-alanine [Nal(1)] and 3-(2-naphthyl)-alanine [Nal(2)]. The l enantiomers of these amino acids were incorporated into the sequence of cholecystokinin in place of the tryptophan in position 30. The cholecystokinin analogues thus obtained behaved as full agonists, with reduced potencies on rat pancreatic acini and on guinea pig brain membranes, by about one order of magnitude for the Nal(2) derivative and by 2 orders of magnitude for the Nal(1) derivative, as compared to the potent parent compound Boc-Tyr(SO 3 H)-Nle-Gly-Trp-Nle-Asp-Phe-NH 2 .