Fig. 1. αβ,α′β′-Diepoxyketones (DEKs) react with nucleophilic cysteine enzymes. (A) Examples of epoxide-bearing drugs. (B) DEK 1 was identified as a potent inhibitor of LdtMt2. (C) Symmetrical DEKs contain 3 potential sites for interactions with nucleophiles, as well as three oxygens that may react with electrophiles. Arrows in teal represent pathways consistent with mechanistic studies. (D) Synthesis of DEKs 1 and 4–11.
