Light-Controlled Tyrosine Nitration of Proteins

Area of Science:

• Biochemistry
• Chemical Biology
• Molecular Biology

Background:

• Protein tyrosine nitration is a key oxidative post-translational modification.
• Existing reagents for protein tyrosine nitration lack efficiency and chemoselectivity, hindering research.

Purpose of the Study:

• To develop a generalizable strategy for light-controlled protein tyrosine nitration.
• To create efficient and chemoselective reagents for modifying tyrosine residues in proteins.

Main Methods:

• Utilized biocompatible dinitroimidazole reagents for nitration.
• Employed 390 nm light irradiation to trigger the reaction.
• Applied the method to peptides, proteins, lasso peptides, and tumor necrosis factor-α.

Main Results:

• Dinitroimidazoles efficiently converted tyrosine to 3-nitrotyrosine residues in peptides and proteins.
• The reaction proceeded with fast kinetics and high chemoselectivity under neutral aqueous conditions.
• Incorporation of 3-nitrotyrosine enhanced lasso peptide thermostability and increased tumor necrosis factor-α immunogenicity.
• Light-controlled time resolution allowed investigation of α-synuclein self-assembly.

Conclusions:

• Developed a novel, light-controlled method for protein tyrosine nitration.
• Demonstrated the utility of dinitroimidazoles as efficient and chemoselective nitration reagents.
• Showcased the impact of tyrosine nitration on protein properties and biological functions.