LATENT INHIBITORS .9. SUBSTRATE ACTIVATED TIME-DEPENDENT INHIBITION OF CARBOXYPEPTIDASE-A BY AMINOCYCLOPROPANECARBOXYLIC ACID-DERIVATIVES AND ANALOGS

A series of 1-aminocyclopropanecarboxylic acid derivatives and analogu es have been synthesised as potential inhibitors of carboxypeptidase A . Whereas simple cyclopropylcarboxamido derivatives of Gly, Phe and Pr o showed no indications of time-dependent, irreversible inhibition, be nzamido-1-aminocyclopropane carboxamido-Phe and Pro were characterised as latent inhibitors. The former was also a substrate for carboxypept idase A but the latter was purely an inhibitor. This behaviour suggest ed that cyclopropylketones should also be inhibitors of carboxypeptida se A; this suggestion was confirmed experimentally. Kinetic experiment s showed surprisingly that the rate of inhibition is increased in the presence of substrate, hippurylphenylalanine. Related secondary alcoho ls also acted as time-dependent inhibitors. The results are evaluated in the context of current views on the mechanism of action of carboxyp eptidase A.