Thrombin Inhibition by the Highly Selective ‘Reversible Suicide Substrate’ N-Ethoxycarbonyl-D-Phenylalanyl-L-Prolyl-α-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-α-azalysine p-nitrophenyl ester (Eoc-D-Phe-ProazaLys- ONp) targeted to the active center of human a-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 α-thrombin competitive inhibitor.