Selective Metal-Site-Guided Arylation of Proteins

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.