Tryptophan oxidation by singlet molecular oxygen [O2(1Deltag)]: mechanistic studies using 18O-labeled hydroperoxides, mass spectrometry, and light emission measurements

Chem Res Toxicol. 2008 Jun;21(6):1271-83. doi: 10.1021/tx800026g. Epub 2008 May 6.

Abstract

Proteins have been considered important targets for reactive oxygen species. Indeed, tryptophan (W) has been shown to be a highly susceptible amino acid to many oxidizing agents, including singlet molecular oxygen [O2(1Deltag)]. In this study, two cis- and trans-tryptophan hydroperoxide (WOOH) isomers were completely characterized by HPLC/mass spectrometry and NMR analyses as the major W-oxidation photoproducts. These photoproducts underwent thermal decay into the corresponding alcohols. Additionally, WOOHs were shown to decompose under heating or basification, leading to the formation of N-formylkynurenine (FMK). Using 18O-labeled hydroperoxides (W18O18OH), it was possible to confirm the formation of two oxygen-labeled FMK molecules derived from W18O18OH decomposition. This result demonstrates that both oxygen atoms in FMK are derived from the hydroperoxide group. In addition, these reactions are chemiluminescent (CL), indicating a dioxetane cleavage pathway. This mechanism was confirmed since the CL spectrum of the WOOH decomposition matched the FMK fluorescence spectrum, unequivocally identifying FMK as the emitting species.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromatography, High Pressure Liquid
  • Hydrogen Peroxide / analysis*
  • Hydrogen Peroxide / chemistry*
  • Kynurenine / analogs & derivatives
  • Kynurenine / chemistry
  • Luminescent Measurements
  • Molecular Structure
  • Oxidation-Reduction
  • Oxygen Isotopes
  • Photochemistry
  • Singlet Oxygen / chemistry*
  • Spectrometry, Mass, Electrospray Ionization
  • Tandem Mass Spectrometry
  • Tryptophan / chemistry

Substances

  • Oxygen Isotopes
  • N'-formylkynurenine
  • Singlet Oxygen
  • Kynurenine
  • Tryptophan
  • Hydrogen Peroxide