Intramolecular addition of cysteine thiyl radical to phenylalanine and tyrosine in model peptides, Phe (CysS*) and Tyr(CysS*): a computational study.

Density Functional Theory (DFT) calculations were carried out to evaluate the potential for intramolecular addition of peptide cysteine (Cys) thiyl radicals (CysS(*)) to aromatic amino acids (Phe and Tyr) in water. These calculations yielded cyclic conformations, in which pi-complexes were more stable than cyclohexadienyl radicals in water. In these pi-complexes, the C(2)-S distances were significantly shorter compared to the C(1)-S and C(3)-S distances. Comparable results on the relative stabilities were obtained for model calculations for the addition of HS(*)/CH(3)S(*) to toluene and p-hydroxytoluene. The adduct of thiyl radicals with Phe was more stable than that with Tyr, and the stabilization energies depended on the C-terminal substituents.