Intramolecular Addition of Cysteine Thiyl Radical to Phenylalanine and Tyrosine in Model Peptides, Phe (CysS<sup>•</sup>) and Tyr(CysS<sup>•</sup>): A Computational Study

2009-04-16T00:00:00Z (GMT) by Sergej Naumov Christian Schöneich
Density Functional Theory (DFT) calculations were carried out to evaluate the potential for <i>intra</i>molecular addition of peptide cysteine (Cys) thiyl radicals (CysS<sup>•</sup>) to aromatic amino acids (Phe and Tyr) in water. These calculations yielded cyclic conformations, in which π-complexes were more stable than cyclohexadienyl radicals in water. In these π-complexes, the C<sub>2</sub>−S distances were significantly shorter compared to the C<sub>1</sub>−S and C<sub>3</sub>−S distances. Comparable results on the relative stabilities were obtained for model calculations for the addition of HS<sup>•</sup>/CH<sub>3</sub>S<sup>•</sup> to toluene and <i>p</i>-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.