Final Products of One-Electron Oxidation of Cyclic Dipeptides Containing Methionine Investigated by IRMPD Spectroscopy: Does the Free Radical Choose the Final Compound?
Yining JiangSuvasthika IndrajithAriel Francis Perez MellorThomas BuergiMarc LecouveyCarine ClavaguéraEnrico BodoChantal Houée-LevinEstelle LoireGiel BerdenJos OomensDebora ScuderiPublished in: The journal of physical chemistry. B (2022)
Reactive oxygen species (ROS) such as hydrogen peroxide (H 2 O 2 ) and the hydroxyl radical ( • OH) have specific functions in biological processes, while their uncontrolled production and reactivity are known to be determining factors in pathophysiology. Methionine (Met) residues act as endogenous antioxidants, when they are oxidized into methionine sulfoxide (MetSO), thus depleting ROS and protecting the protein. We employed tandem mass spectrometry combined with IR multiple photon dissociation spectroscopy to study the oxidation induced by OH radicals produced by γ radiolysis on model cyclic dipeptides c(LMetLMet), c(LMetDMet), and c(GlyMet). Our aim was to characterize the geometries of the oxidized peptides in the gas phase and to understand the relationship between the structure of the 2-center 3-electron (2c-3e) free radical formed in the first step of the oxidation process and the final compound. Density functional theory calculations were performed to characterize the lowest energy structures of the final product of oxidation and to interpret the IR spectra. Collision-induced dissociation tandem mass spectrometry (CID-MS 2 ) experiments of oxidized c(LMetLMet)H + and c(LMetDMet)H + led to the loss of one or two oxidized sulfenic acid molecules, indicating that the addition of one or two oxygen atoms occurs on the sulfur atom of both methionine side chains and no sulfone formation was observed. The CID-MS 2 fragmentation mass spectrum of oxidized c(GlyMet)H + showed only the loss of one oxidized sulfenic acid molecule. Thus, the final products of oxidation are the same regardless of the structure of the precursor sulfur-centered free radical.
Keyphrases
- hydrogen peroxide
- tandem mass spectrometry
- electron transfer
- density functional theory
- low density lipoprotein
- ultra high performance liquid chromatography
- liquid chromatography
- high performance liquid chromatography
- high resolution
- reactive oxygen species
- mass spectrometry
- gas chromatography
- molecular dynamics
- simultaneous determination
- nitric oxide
- amino acid
- multiple sclerosis
- solid phase extraction
- ms ms
- dna damage
- cell death
- high resolution mass spectrometry
- single molecule
- diabetic rats
- high glucose
- molecular dynamics simulations
- oxidative stress
- small molecule
- endothelial cells
- binding protein
- electron microscopy