AI Article Synopsis
- The research introduces a new method called "seleno-click" to create amide-linked inhibitors targeting the protein Mcl-1, building on a previous technique known as kinetic target-guided synthesis (KTGS).
- This new seleno-click approach utilizes the high reactivity of selenocarboxylates to improve the reaction with electron-rich azides, broadening the potential applications of KTGS.
- The effectiveness of this method is illustrated by producing a specific Mcl-1 inhibitor at both 37 °C and a lower temperature of 4 °C, indicating its usefulness for sensitive biological targets.
Article Abstract
Capitalizing on our previous kinetic target-guided synthesis (KTGS) involving the sulfo-click reaction to form -acylsulfonamide-linked inhibitors in the presence of the protein-protein interaction target Mcl-1, we herein report a seleno-click approach for amide-linked inhibitors of Mcl-1. The seleno-click reaction leverages the enhanced reactivity of selenocarboxylates, enabling the templated amidation with electron-rich azides, thereby expanding the scope of KTGS. The potential of this approach is demonstrated by generating -benzyl-5-(4-isopropylthiophenol)-2-hydroxyl nicotinamide, a known Mcl-1 inhibitor featuring an amide, KTGS at 37 °C against Mcl-1. Notably, the seleno-click strategy was also effective at 4 °C, offering a variant for thermally sensitive biological targets.
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| http://dx.doi.org/10.1039/d4cc04491f | DOI Listing |
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