Ubiquitin- Vinylmethyl ester

Ub-VME is synthesized by the conjugation of 4-amino-but-2-enoic methyl ester to the C-terminus of UbiquitindeltaG76. Binding of ubiquitin by deubiquitylases (DUBs), for instance UCH’s and most USPs, positions the reactive vinyl bond next to the sulfhydryl-group of the active site cysteine. Nucleophilic attack by the sulfhydryl on the vinyl bond produces a stable, covalent thioether bond between Ubiquitin and the deubiquitylase. Thus Ub-VME is a potent suicide inhibitor of DUBs.