1245941-14-3Relevant academic research and scientific papers
Michael acceptor-containing coenzyme a analogues as inhibitors of the atypical coenzyme a disulfide reductase from staphylococcus aureus
Van Der Westhuyzen, Renier,Strauss, Erick
supporting information; experimental part, p. 12853 - 12855 (2010/11/05)
Coenzyme A (CoA) analogues containing α,β-unsaturated ester, ketone, and sulfone moieties were prepared by chemo-enzymatic synthesis as inhibitors of coenzyme A disulfide reductase (CoADR), a proven and as yet unexploited drug target in Staphylococcus aureus. Among these Michael acceptor-containing CoA analogues, which were designed to target CoADR's single essential active site cysteine for conjugate addition, a phenyl vinyl sulfone-containing analogue showed the most potent inhibition with a competitive Ki of ～40 nM, and time-dependent inactivation with a second-order rate of inactivation constant of ～40 000 s -1?M-1. Our results suggest that electrophilic substrate analogues should be considered as potential inhibitors of other medicinally relevant disulfide reductase enzymes.
