Toward Site Specificity of Oxidative Damage in Proteins: C−H and C−C Bond Dissociation Energies and Reduction Potentials of the Radicals of Alanine, Serine, and Threonine ResiduesAn ab Initio Study

Abstract

High-level ab initio computations were used to characterize the parent species and αC radicals for alanine, serine, and threonine, both as free neutral amino acids (AH) and as residues in model peptides (PH) intended to mimic the midchain environment in proteins. The ab initio energies were used in isodesmic reactions to predict bond dissociation energies (BDEs, DαCH) at 298 K, in kJ mol-1, to an estimated accuracy of ±10 kJ mol-1. For the fully optimized systems the values of DαCH are AH(Gly), 331; AH(Ala), 317; AH(Ser), 327; AH(Thr), 328; PH(Gly), 348; PH(Ala), 344; PH(Ser), 348; PH(Thr), 356. All of the DαCH values are less than the BDE of a typical SH bond (370 kJ mol-1), as in cysteine or glutathione (GSH), a result that suggests that oxidative damage at the αC site will not be repaired efficiently by the mechanism of H donation from GSH. Values of DαCH in typical peptide conformations, such as β-sheet and α-helical secondary structure, were estimated by constraining the Ramachandran dihedral angles,...