Study of a lipophilic captopril analogue binding to angiotensin I converting enzyme.
Human ACE is a central component of the renin-angiotensin system and a major therapeutic target for cardiovascular diseases. The somatic form of the enzyme (sACE) comprises two homologous metallopeptidase domains (N and C), each bearing a zinc active site with similar but distinct substrate and inhibitor specificities. In this study, we present the biological activity of silacaptopril, a silylated analogue of captopril, and its binding affinity towards ACE. Based on the recently determined crystal structures of both the ACE domains, a series of docking calculations were carried out in order to study the structural characteristics and the binding properties of silacaptopril and its analogues with ACE.
Dalkas
Georgios A
GA
Department of Pharmacy, University of Patras, Panepistimioupoli-Rion, GR-26504, Greece.
Marchand
Damien
D
Galleyrand
Jean-Claude
JC
Martinez
Jean
J
Spyroulias
Georgios A
GA
Cordopatis
Paul
P
Cavelier
Florine
F
D002216:Captopril / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D020134:Catalytic Domain; D003198:Computer Simulation; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D017646:Organosilicon Compounds / Q000737:chemistry* / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding
D004791:Enzyme Inhibitors; D017646:Organosilicon Compounds; C549228:silacaptopril; D002216:Captopril; D007703:Peptidyl-Dipeptidase A