Thrombin inhibition by the highly selective 'reversible suicide substrate' N-ethoxycarbonyl-D-phenylalanyl-L-prolyl-alpha-azalysine p-nitrophenyl ester.
Thrombin is the last enzyme in the blood coagulation cascade. All pharmacological aspects support the use of thrombin inhibitors as antithrombotic agents. Here, we review the unusual inhibition behavior of the highly selective 'reversible suicide substrate' N-ethoxycarbonyl-D-phenylalanyl-L-prolyl-alpha-azalysine p-nitrophenyl ester (Eoc-D-Phe-Pro-azaLys-ONp) targeted to the active center of human alpha-thrombin. Eoc-D-Phe-Pro-azaLys-ONp is an acylating agent, but its hydrolysis product 1(N-ethoxycarbonyl-D-phenylalanyl-L-prolyl)-2(4-aminobutyl) hydrazine behaves as a highly selective human alpha-thrombin competitive inhibitor.
Ascenzi
Paolo
P
Department of Biology and Interdepartmental Laboratory for Electron Microscopy, University Roma Tre, Viale Marconi 446, I-00146 Roma, Italy. ascenzi@uniroma3.it
Gallina
Carlo
C
Bolognesi
Martino
M
D006801:Humans; D006834:Hydrazines; D007700:Kinetics; D009842:Oligopeptides / Q000502:physiology*; D013816:Thermodynamics; D013917:Thrombin / Q000378:metabolism*
D006834:Hydrazines; C101147:N-ethoxycarbonyl-phenylalanyl-prolyl-alpha-azalysine 4-nitrophenyl ester; D009842:Oligopeptides; D013917:Thrombin