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

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 (k1 and k−1) and the binding equilibrium constant (Ka) were estimated to be k1 = 4.1 × 106 L mol−1 s−1, k−1 = 7.3 × 10−3 s−1 and Ka = 5.62 × 108 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.