Degrasyn inhibits deubiquitination enzymes and has anti-cancer activity. We here show that it also exhibits antimicrobial activity against multi-resistant Staphylococcus aureus. Structure activity relationship studies demonstrate animportant role of the electrophilic -cyanoacrylamide moietyas Michael acceptor. A suite of chemical proteomic techniques unraveled binding of this moiety to various cysteine residues of essential proteins in a reversibly covalent manner.
Lee, K.M., Le, P., Sieber, S.A.*, Hacker, S.M.*, "Degrasyn exhibits antibiotic activity against multi-resistant Staphylococcus aureus by modifying several essential cysteines",
Chem. Commun., 2020
Reproduced with permission.