Bradykinin analogs as inhibitors of angiotensin-converting enzyme.

A series of peptide analogs and fragments of bradykinin were designed and synthesized on solid supports using Boc and Fmoc strategies, and on polyethylene pins using Fmoc strategy. The peptides were purified, characterized and tested for their inhibitory effects on angiotensin-converting enzyme. The inhibition of the converting enzyme. The inhibition of the enzyme was measured spectrophotometrically using Furylacryloyl-Phe-Gly-Gly as the substrate. Apparent Ki's were determined for the substrates, which exhibited significant inhibition in the initial screening assay using 10 microM of the peptide inhibitor. Short peptides corresponding to the carboxyl terminus of bradykinin were found to be poor inhibitors of angiotensin-converting enzyme. However, bradykinin-like peptides with modifications at their amino terminus are effective inhibitors. The best inhibitor found in this study, Ala2,6-des-Pro3-bradykinin, has an apparent Ki of 30.2 nM, compared to an apparent Ki of 94 nM for des-Pro3-bradykinin, which was reported to be a better inhibitor of angiotensin-converting enzyme than captopril.