Inhibition of thermolysin and human α-thrombin by cobalt(III) Schiff base complexes

Toshihiko Takeuchi, Arnd Böttcher, Cindy M. Quezada, Thomas J. Meade*, Harry B. Gray

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

85 Scopus citations

Abstract

Cobalt(III) Schiff base complexes have been shown to inhibit the replication of the ocular herpes virus. It is well known that these complexes have a high affinity for nitrogenous donors such as histidine residues, and it is possible that they bind to (and inhibit) an enzyme that is crucial to viral replication. In model studies, we have found that [Co(acacen)(NH3)2]+ is an effective irreversible inhibitor of thermolysin at millimolar concentrations; it also inhibits human α-thrombin. Axial ligand exchange with an active-site histidine is the proposed mechanism of inhibition. The activity of thermolysin and thrombin can be protected by binding a reversible inhibitor to the active site before addition of the cobalt(III) complex. Copyright (C) 1999 Elsevier Science Ltd.

Original languageEnglish (US)
Pages (from-to)815-819
Number of pages5
JournalBioorganic and Medicinal Chemistry
Volume7
Issue number5
DOIs
StatePublished - May 1 1999

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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