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.
Andújar-Sánchez
Montserrat
M
Dpto. Química Física, Bioquímica y Química Inorgánica, Universidad de Almería, Carretera Sacramento s/n, Almería 04120, Spain.
Jara-Pérez
Vicente
V
Cámara-Artigas
Ana
A
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D002151:Calorimetry; D018360:Crystallography, X-Ray; D004151:Dipeptides / Q000737:chemistry / Q000378:metabolism; D006358:Hot Temperature; D008958:Models, Molecular; D007703:Peptidyl-Dipeptidase A / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D013816:Thermodynamics; D017186:Titrimetry
D000806:Angiotensin-Converting Enzyme Inhibitors; D004151:Dipeptides; C045207:aspartyl-phenylalanine; D007703:Peptidyl-Dipeptidase A