Angiotensin-converting enzyme inhibitors: synthesis and biological activity of acyltripeptide analogs of enalapril

Publisher Website
Google Scholar
Abstract
The synthesis and biological activity of a series of inhibitors of angiotensin-converting enzyme (EC 3.4.15.1) are described. Incorporation of the substituted N-carboxymethyl dipeptide design of enalapril (MK-421) into acyl tripeptides and larger peptides yielded potent inhibitors of the enzyme. These can be viewed as substrates analogs in which the carbonyl of the scissile peptide bond is replaced by a CHCO2H group. Several of the analogs described possess inhibitory potency equal to that of enalaprilat (MK-422), but none achieves an increase in potency which would demonstrate additional binding interactions contributed by the extended peptide chain. Application of the design described may be useful for inhibition of other metallopeptidases.