Tuesday, May 29, 2018

The Nitro Group as a Masked Electrophile in Covalent Enzyme Inhibition

ACS Chem. Biol., 2018
DOI: 10.1021/acschembio.8b00225

We report the unprecedented reaction between a nitroalkane and an active-site cysteine residue to yield a thiohydroximate adduct. Structural and kinetic evidence suggests the nitro group is activated by conversion to its nitronic acid tautomer within the active site. The nitro group, therefore, shows promise as a masked electrophile in the design of covalent inhibitors targeting binding pockets with appropriately placed cysteine and general acid residues

Synthesis and functionalization of vinyl sulfonimidamides and their potential as electrophilic warheads

Yu Tung Wong,  Charles Bell, and  Michael C. Willis Chem. Sci., 2025 DOI https://doi.org/10.1039/D5SC02420J Covalent inhibitor design is dom...