Synthesis and evaluation of peptidic maleimides as transglutaminase inhibitors

A series of novel transglutaminase inhibitors was prepared, based on the scaffold of a commonly used peptide substrate and bearing an electrophilic maleimide group. These compounds were evaluated in vitro and shown to lead to irreversible inactivation of tissue transglutaminase. Comparison with inhibitors studied previously provides insight into the steric environment of the enzyme active site.

Graphical abstractA series of novel peptidic maleimide inhibitors of transglutaminase was prepared and evaluated as irreversible inhibitors of transglutaminase.Figure optionsDownload full-size imageDownload as PowerPoint slide