Imidazolium-based warheads strongly influence activity of water-soluble peptidic transglutaminase inhibitors

Eduard Badarau, Alexandre Mongeot, Russell Collighan, Dan Rathbone, Martin Griffin

Research output: Contribution to journalArticle

Abstract

New peptidic water-soluble inhibitors are reported. In addition to the carboxylate moiety, a new polar warhead was explored. Depending on the size of its substituents, the newly appended imidazolium scaffold designed to enhance the hydrophilic character of the inhibitors could induce a good inhibition for tissue transglutaminase (TG2) and blood coagulation factor XIIIa (FXIIIa). Correlated with the narrow tunnel that hosts the target catalytic cysteine residue, the various modulations suggest a bent conformation of the ligands as the binding pattern mode. Analogues in the dialkylsulfonium series were also tested and showed specificity for TG2 over FXIIIa.

LanguageEnglish
Pages526-530
Number of pages5
JournalEuropean Journal of Medicinal Chemistry
Volume66
Early online date7 Jun 2013
DOIs
Publication statusPublished - Aug 2013

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Factor XIIIa
Transglutaminases
Blood Coagulation Factors
Water
Scaffolds
Cysteine
Conformations
Tunnels
Modulation
Ligands
transglutaminase 2

Bibliographical note

Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Keywords

  • coagulation factor XIIIa (FXIIIa)
  • dialkylsulfonium
  • imidazolium warheads
  • peptidic inhibitors
  • tissue transglutaminase (TG2)

Cite this

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AU - Griffin, Martin

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