Thermodynamic determination of the binding constants of angiotensin-converting enzyme inhibitors by a displacement method.
Somatic angiotensin I-converting enzyme (s-ACE) plays a central role in blood pressure regulation and has been the target of most antihypertensive drugs. A displacement isothermal titration calorimetry method has been used to accurately determine the binding constant of three strong s-ACE inhibitors. Under the experimental conditions studied in this work, the relative potency of the inhibitors was determined to be enalaprilat>lisinopril>captopril. We analyze the thermodynamic behaviour of the binding process using the new structural information provided by the ACE structures, as well as the conformational changes that occur upon binding.
T1 T2 T3 T4 T5 T6 T7 T8 T9 T10
CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y
enalaprilat lisinopril captopril angiotensin I angiotensin ACE ACE ACE angiotensin I-converting enzyme angiotensin-converting enzyme