Inhibitors of tissue transglutaminase

Jeffrey W Keillor; Kim Y P Apperley; Abdullah Akbar

doi:10.1016/j.tips.2014.10.014

Inhibitors of tissue transglutaminase

Trends Pharmacol Sci. 2015 Jan;36(1):32-40. doi: 10.1016/j.tips.2014.10.014. Epub 2014 Dec 12.

Authors

Jeffrey W Keillor¹, Kim Y P Apperley², Abdullah Akbar²

Affiliations

¹ Department of Chemistry, University of Ottawa, 10 Marie-Curie, Ottawa, ONT, K1N 6N5, Canada. Electronic address: jkeillor@uottawa.ca.
² Department of Chemistry, University of Ottawa, 10 Marie-Curie, Ottawa, ONT, K1N 6N5, Canada.

PMID: 25500711
DOI: 10.1016/j.tips.2014.10.014

Abstract

Tissue transglutaminase (TG2) catalyzes the cross-linking of proteins by the formation of isopeptide bonds between glutamine (Gln) and lysine (Lys) side chains. Although TG2 is essential for the stabilization of the extracellular matrix, its unregulated activity has been implicated in celiac disease, fibrosis, and cancer metastasis, among other disorders. Given the importance and range of TG2-related pathologies, recent work has focused on the development of potent and selective inhibitors against TG2. In this review, we present the latest and most noteworthy irreversible and reversible inhibitors of TG2, and offer perspectives for the design of future inhibitors, in the hope that lead compounds with therapeutic potential may soon be discovered.

Keywords: TG2; cross-link; enzyme inhibition; irreversible inhibitor; reversible inhibitor; tissue transglutaminase.

Publication types

Review

MeSH terms

Animals
Enzyme Inhibitors / pharmacology
Enzyme Inhibitors / therapeutic use
Humans
Protein Conformation
Transglutaminases / antagonists & inhibitors*
Transglutaminases / chemistry
Transglutaminases / metabolism

Substances

Enzyme Inhibitors
Transglutaminases