Ketomethyldipeptides I. A new class of angiotensin converting enzyme inhibitors

The design rationale for a new series of angiotensin-converting enzyme (ACE) inhibitors which incorporate a ketone substituent into a peptide backbone is described. Molecular regions which were expected to mimic the binding of an N-acyl tripeptide substrate at secondary binding sites S 1 and S 1′ were systematically varied in order to study the specificity of inhibitor binding and optimize inhibition against ACE. The most effective ketomethyldipeptides inhibit ACE in the 10 −9 M range.