MERCAPTOACYL AMINO-ACID INHIBITORS OF ATRIOPEPTIDASE .1. STRUCTURE-ACTIVITY RELATIONSHIP STUDIES OF METHIONINE AND S-ALKYLCYSTEINE DERIVATIVES

A broad series of N-(3-mercaptoacyl) amino acid derivatives was evalua ted for their ability to inhibit atriopeptidase (neutral endopeptidase , EC 3.4.24.11) in vitro and in vivo. Structural parameters studied we re (i) the substituent on the 2-position of the 3-mercaptopropionyl mo iety, (ii) the amino acid component, (iii) the S-terminal derivative, and (iv) the C-terminal derivative. Optimum activity was observed for derivatives of methionine and S-alkylcysteines. [(2-methylphenyl)methy l]-1-oxopropyl]-L-methionine was identified as a highly effective inhi bitor of atriopeptidase meriting evaluation as a potential cardiovascu lar therapeutic agent.