Toward understanding the protein oxidation processes: OH addition on tyrosine, phenylalanine, or methionine?

Oxidation of peptides and proteins by •OH radicals produced in oxidative stress or in radiotherapy, accidental irradiations, etc., is well known to form oxidative metabolites that are responsible for numerous diseases including neurodegenerative pathologies. Tyrosine (Tyr), Phenylalanine (Phe), and Methionine (Met) residues are known to be the major targets of •OH radicals. This study aims at better understanding the •OH addition process on these three amino acids. On the basis of different amino acid prototypes, the Gibbs energy (ΔG) (B3P86/6‐31+G(d,p)) and rate constants (kTST) (MPWB1K/6‐31+G(d,p)) of •OH addition were calculated. The •OH addition capacity was studied (i) on the different positions of the aromatic rings of Tyr and Phe and (ii) on the S‐atom of Met. The addition was favored on the aromatic rings of Tyr and Phe with almost the same ΔGaddition values for both amino acids. No preferential position was found. The only parameter that may influence the OH‐adduct formation is the presence or absence of intra‐H bondings. In agreement with the experimental data available from the literature, the OH‐adduct on Met appeared to be less favored. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2011