αβ,α′β′-Diepoxyketones are mechanism-based inhibitors of nucleophilic cysteine enzymes
Mariska de Munnik, Jasper Lithgow, Lennart Brewitz, Kirsten E. Christensen, Robert H. Bates, Beatriz Rodríguez-Miquel, Christopher J. Schofield
Abstract
αβ,α′β′-Diepoxyketones (DEKs) inhibit nucleophilic cysteine enzymes. DEKs react with a transpeptidase and the SARS-CoV-2 main protease via epoxide opening; retro-aldol and other reactions can then occur, enabling irreversible alkylation.
Topics & Concepts
CysteineNucleophileChemistryMechanism (biology)EnzymeCombinatorial chemistryBiochemistryStereochemistryCatalysisPhysicsQuantum mechanicsPeptidase Inhibition and AnalysisClick Chemistry and ApplicationsAdenosine and Purinergic Signaling