1.
Chem Commun (Camb)
; 59(86): 12859-12862, 2023 Oct 26.
Artículo
en Inglés
| MEDLINE
| ID: mdl-37815791
RESUMEN
Epoxides are an established class of electrophilic alkylating agents that react with nucleophilic protein residues. We report αß,α'ß'-diepoxyketones (DEKs) as a new type of mechanism-based inhibitors of nucleophilic cysteine enzymes. Studies with the L,D-transpeptidase LdtMt2 from Mycobacterium tuberculosis and the main protease from SARS-CoV-2 (Mpro) reveal that following epoxide ring opening by a nucleophilic cysteine, further reactions can occur, leading to irreversible alkylation.