Thrombin Inhibition by the Highly Selective ‘ Reversible Suicide Substrate ’ N-Ethoxycarbonyl-D-Phenylalanyl-L-Prolyl-α-Azalysine p-Nitrophenyl Ester

Title: Thrombin Inhibition by the Highly Selective ‘ Reversible Suicide Substrate ’ N-Ethoxycarbonyl-D-Phenylalanyl-L-Prolyl-α-Azalysine p-Nitrophenyl Ester

Volume: 12 Issue: 5

Author(s): Paolo Ascenzi, Carlo Gallina and Martino Bolognesi

Affiliation:

Keywords: human thrombin, catalytic and inhibition mechanism, substrate and inhibitor recognition, suicide substrate, structural aspects, kinetics, thermodynamics

Abstract: 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.

Cite this article as:

Ascenzi Paolo, Gallina Carlo and Bolognesi Martino, Thrombin Inhibition by the Highly Selective ‘ Reversible Suicide Substrate ’ N-Ethoxycarbonyl-D-Phenylalanyl-L-Prolyl-α-Azalysine p-Nitrophenyl Ester, Protein & Peptide Letters 2005; 12(5) . https://dx.doi.org/10.2174/0929866054395301