Selective inhibition of human mast cell tryptase by gabexate mesylate, an antiproteinase drug

Fulvio Erba, Laura Fiorucci, Stefano Pascarella, Enea Menegatti, Paolo Ascenzi, Franca Ascoli

Research output: Contribution to journalArticlepeer-review

Abstract

Gabexate mesylate is a non-antigenic synthetic inhibitor of trypsin-like serine proteinases that is therapeutically used in the treatment of pancreatitis and disseminated intravascular coagulation and as a regional anticoagulant for hemodialysis. Considering the structural similarity between gabexate mesylate and arginine-based inhibitors of trypsin-like serine proteinases, the effect of gabexate mesylate on human and bovine mast cell tryptase action was investigated. Values of the inhibition constant (K i) for gabexate mesylate binding to human and bovine tryptase were 3.4 × 10 -9 M and 1.8 × 10 -7 M (at pH 7.4 and 37.0°), respectively. Furthermore, gabexate mesylate inhibited the fibrinogenolytic activity of human tryptase. On the basis of the available x-ray crystal structure of human tryptase, the possible binding mode of gabexate mesylate to human and bovine tryptase was analyzed. Human tryptase inhibition by gabexate mesylate may account for the reported prevention of inflammation, erosion, and ulceration of skin and mucosae.

Original languageEnglish
Pages (from-to)271-276
Number of pages6
JournalBiochemical Pharmacology
Volume61
Issue number3
DOIs
Publication statusPublished - Feb 1 2001

Keywords

  • Bovine tryptase
  • Enzyme inhibition
  • Gabexate mesylate
  • Human tryptase
  • Structural aspects

ASJC Scopus subject areas

  • Pharmacology

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