Kinetic properties of the angiotensin converting enzyme inhibitor ramiprilat

Abstract

The interaction of angiotensin converting enzyme (ACE) with ramiprilat was studied at pH 7.5 in the presence of 300 mmol/l sodium chloride with furanacryloyl-Phe-Gly-Gly as substrate. Ramiprilat inhibits ACE with a Ki value of 7 pmol/l. It is both a slow- and tight-binding inhibitor; the mode of inhibition is fully competitive. Binding of ramiprilat to ACE proceeds by a two-step mechanism E + I in equilibrium EI in equilibrium EI* in which the inhibitor rapidly binds to enzyme to form an initial enzyme-inhibitor complex, which then undergoes a slow isomerization. The interaction of ramiprilat with ACE is compared to that of two other potent inhibitors, captopril and enalaprilat.