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

A chemoproteomic atlas of the human purine interactome for regioselective ligand discovery

Zhihong Li, Hsiao-Kuei Tsai, Adam H. Libby, Michael W. Founds, Olivia L. Murtagh, Madeleine L. Ware, David M. Leace, Wesley J. Wolfe, Philli...