35 MHz quartz crystal microbalance and surface plasmon resonance studies on the binding of angiotensin converting enzyme with lisinopril

Abstract

Angiotensin converting enzyme (ACE) plays a pivotal role in blood pressure regulation, and its interaction with an ACE inhibitor (ACEI) is an important research topic for treatment of hypertension. Herein, a low reagent consumption, multiparameter and highly sensitive quartz crystal microbalance (QCM) at 35-MHz fundamental frequency was utilized to monitor in situ the binding process of solution lisinopril (LIS, a carboxylic third-generation ACEI) to ACE adsorbed at a 1-dodecanethiol (C12SH)-modified Au electrode. From the QCM data, the binding molar ratio (r) of LIS to adsorbed ACE was estimated to be 2.3:1, and the binding and dissociation rate constants (k(1) and k(-1)) and the binding equilibrium constant (K(a)) were estimated to be k(1)=4.1×10(6) L mol(-1) s(-1), k(-1)=7.3×10(-3) s(-1) and K(a)=5.62×10(8) L mol(-1), respectively. Comparable qualitative and quantitative results were also obtained from separate experiments of cyclic voltammetry, electrochemical impedance spectroscopy and surface plasmon resonance measurements.