Identification and relative quantification of tyrosine nitration in a model peptide using two-dimensional infrared spectroscopy

Lays Rezende Valim, Julia A. Davies, Karina Tveen Jensen, Rui Guo, Keith R. Willison, Corinne M. Spickett, Andrew R. Pitt, David R. Klug*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Nitration of tyrosine in proteins and peptides is a post-translational modification that occurs under conditions of oxidative stress. It is implicated in a variety of medical conditions, including neurodegenerative and cardiovascular diseases. However, monitoring tyrosine nitration and understanding its role in modifying biological function remains a major challenge. In this work, we investigate the use of electron-vibration-vibration (EVV) two-dimensional infrared (2DIR) spectroscopy for the study of tyrosine nitration in model peptides. We demonstrate the ability of EVV 2DIR spectroscopy to differentiate between the neutral and deprotonated states of 3-nitrotyrosine, and we characterize their spectral signatures using information obtained from quantum chemistry calculations and simulated EVV 2DIR spectra. To test the sensitivity of the technique, we use mixed-peptide samples containing various levels of tyrosine nitration, and we use mass spectrometry to independently verify the level of nitration. We conclude that EVV 2DIR spectroscopy is able to provide detailed spectroscopic information on peptide side-chain modifications and to detect nitration levels down to 1%. We further propose that lower nitration levels could be detected by introducing a resonant Raman probe step to increase the detection sensitivity of EVV 2DIR spectroscopy. (Graph Presented).

Original languageEnglish
Pages (from-to)12855-12864
Number of pages10
JournalJournal of Physical Chemistry: Part B
Volume118
Issue number45
Early online date27 Oct 2014
DOIs
Publication statusPublished - 13 Nov 2014

Bibliographical note

This is an Open Access article published under a Creative Commons Attribution (CC-BY) License, which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.

Funding: EPSRC (Grant EP/I017887/1 and EP/J500239/1)

Supporting information available on the journal website.

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