AI Article Synopsis
- Peptide epoxyketones are effective and specific inhibitors of the proteasome, targeting its active sites.
- The selectivity of these inhibitors comes from their unique structure, particularly the epoxyketone dual electrophilic warhead that reacts with a key amino acid in the proteasome.
- Research demonstrated that while the carbonyl component of the warhead is crucial for effectiveness, modifications can include replacing the adjacent epoxide with another carbonyl, though this significantly reduces the inhibitor’s activity.
Article Abstract
Peptide epoxyketones are potent and selective proteasome inhibitors. Selectivity is governed by the epoxyketone dual electrophilic warhead, which reacts with the N-terminal threonine 1,2-amino alcohol uniquely present in proteasome active sites. We studied a series of C-terminally modified oligopeptides featuring adjacent electrophiles based on the epoxyketone warhead. We found that the carbonyl moiety in the natural warhead is essential, but that the adjacent epoxide can be replaced by a carbonyl, though with considerable loss of activity.
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| http://dx.doi.org/10.1039/c4ob00893f | DOI Listing |
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