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.
Keywords: human thrombin, catalytic and inhibition mechanism, substrate and inhibitor recognition, suicide substrate, structural aspects, kinetics, thermodynamics
Protein & Peptide Letters
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.
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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
DOI https://dx.doi.org/10.2174/0929866054395301 |
Print ISSN 0929-8665 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5305 |
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