title: Inhibitors of tissue transglutaminase.
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.
authors.affiliation: Department of Chemistry, University of Ottawa, 10 Marie-Curie, Ottawa, ONT, K1N 6N5, Canada. Electronic address: jkeillor@uottawa.ca.
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Keillor
authors.affiliation: Department of Chemistry, University of Ottawa, 10 Marie-Curie, Ottawa, ONT, K1N 6N5, Canada.
authors.forename: Kim Y P
authors.initials: KY
authors.lastname: Apperley
authors.affiliation: Department of Chemistry, University of Ottawa, 10 Marie-Curie, Ottawa, ONT, K1N 6N5, Canada.
authors.forename: Abdullah
authors.initials: A
authors.lastname: Akbar
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D011487:Protein Conformation; D011503:Transglutaminases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D011503:Transglutaminases
keywords: TG2; cross-link; enzyme inhibition; irreversible inhibitor; reversible inhibitor; tissue transglutaminase