Open AccessKinetic Properties of the Angiotensin Converting Enzyme Inhibitor Ramiprilat
Author(s) -
Peter Bünning
Publication year - 1987
Publication title -
journal of cardiovascular pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.762
H-Index - 100
eISSN - 1533-4023
pISSN - 0160-2446
DOI - 10.1097/00005344-198706107-00005
Subject(s) - enalaprilat , chemistry , captopril , angiotensin converting enzyme , enzyme inhibitor , ace inhibitor , enzyme , non competitive inhibition , ramipril , enalapril , stereochemistry , pharmacology , biochemistry , endocrinology , biology , blood pressure
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.