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Imidazolium-based warheads strongly influence activity of water-soluble peptidic transglutaminase inhibitors
Eduard Badarau1, Alexandre Mongeot, Russell Collighan
1School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UK.
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.
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