Light-controlled Tyrosine Nitration of Proteins.

Tyrosine nitration of proteins represents one of the most important oxidative post-translational modifications in vivo and is closely related to human physiology, pathology and aging. A major obstacle for its biochemical and physiological studies is the lack of efficient and chemoselective protein tyrosine nitration reagents. Herein, we report a generalizable strategy for light-controlled protein tyrosine nitration by employing biocompatible dinitroimidazole reagents. Upon 390 nm irradiation, dinitroimidazoles efficiently convert tyrosine residues into 3-nitrotyrosine residues in peptides and proteins with fast kinetics and high chemoselectivity under neutral aqueous buffer conditions. We demonstrate that the incorporation of 3-nitrotyrosine residues enhances the thermostability of lasso peptide natural products and endows murine tumor necrosis factor-α with strong immunogenicity to break self-tolerance. Furthermore, the light-controlled time-resolution of this method allows the investigation of the impact of tyrosine nitration on the self-assembly behavior of α-synuclein.