Writing, Erasing, and Transferring Phosphoryl Groups through Reagent-Regenerating Chemical (De)Phosphorylation

Existing chemical phosphorylation methods have remained inherently one-way processes, because phosphoryl-group installation either transforms the phosphorylating reagent by changing its oxidation state or consumes hydrolytically labile reactive species, thereby precluding regeneration of the active phosphorylating reagent. Herein, we report the chemical (de)phosphorylation platform in which phosphorylation of histidine and heteroatom nucleophiles is reversed, regenerating both the substrate and the phosphorylating reagent. This switchability further enables phosphoryl-group transfer or rephosphorylation reactions.