Evidence for the Prerequisite Formation of Phenoxyl Radicals in Radical-Mediated Peptide Tyrosine Nitration In Vacuo

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal

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Original languageEnglish
Pages (from-to)331-335
Journal / PublicationChemistry - A European Journal
Volume26
Issue number1
Online published28 Oct 2019
Publication statusPublished - 2 Jan 2020

Abstract

The elementary mechanism of radical-mediated peptide tyrosine nitration, which is a hallmark of post-translational modification of proteins under nitrative stress in vivo, has been elucidated in detail by using an integrated approach that combines the gas-phase synthesis of prototypical molecular tyrosine-containing peptide radical cations, ion–molecule reactions, and isotopic labeling experiments with DFT calculations. This reaction first involves the radical recombination of .NO2 towards the prerequisite phenoxyl radical tautomer of a tyrosine residue, followed by proton rearrangements, finally yielding the stable and regioselective 3-nitrotyrosyl residue product. In contrast, nitration with the π-phenolic radical cation tautomer is inefficient. This first direct experimental evidence for the elementary steps of the radical-mediated tyrosine nitration mechanism in the gas phase provides a fundamental insight into the regioselectivity of biological tyrosine ortho-nitration.

Research Area(s)

  • isomerization, nitration, radical reactions, reaction mechanisms, regioselectivity