Selective Metal-Site-Guided Arylation of Proteins

• DOI: 10.1021/jacs.6b04043
• Publication Date: 2016-06-23T23:24:11Z
• Authors: Jens Willwacher; Ritu Raj; Shabaz Mohammed; Benjamin G. Davis
• Keywords: Models, Molecular; Binding Sites; Protein Conformation; Rhodothermus; Hydrocarbons, Aromatic; Mannosyltransferases; 01 natural sciences; Catalysis; Palladium; 0104 chemical sciences

We describe palladium-mediated S-arylation that exploits natural metal-binding motifs to ensure high site selectivity for a proximal reactive residue. This allows the chemical identification not only of proteins that bind metals but also the environment of the metal-binding site itself through proteomic analysis of arylation sites. The transformation is easy to perform under standard conditions, does not require the isolation of a reactive Ar-Pd complex, is broad in scope, and is applicable in cell lysates as well as to covalent inhibition/modulation of metal-dependent enzymatic activity.