Thrombin inhibition by the highly selective 'reversible suicide substrate' N-ethoxycarbonyl-D-phenylalanyl-L-prolyl-α-azalysine p-nitrophenyl ester

Paolo Ascenzi, Carlo Gallina, Martino Bolognesi

Research output: Contribution to journalArticlepeer-review

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-Pro-azaLys-ONp) targeted to the active center of human α-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.

Original languageEnglish
Pages (from-to)433-438
Number of pages6
JournalProtein and Peptide Letters
Volume12
Issue number5
DOIs
Publication statusPublished - Jul 2005

Keywords

  • Catalytic and inhibition mechanism
  • Human α-thrombin
  • Kinetics
  • Structural aspects
  • Substrate and inhibitor recognition
  • Suicide substrate
  • Thermodynamics

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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