5,6-dihydropyrimidine peroxyl radical reactivity in DNA

Abstract

Nucleobase radicals are a major family of reactive species produced in DNA as a result of oxidative stress. Two such radicals, 5-hydroxy-5,6- dihydrothymidin-6-yl radical (1) and 5,6-dihydrouridin-6-yl radical (5), were independently generated within chemically synthesized oligonucleotides from photochemical precursors. Neither nucleobase radical produces direct strand breaks or alkali-labile lesions in single or double stranded DNA. The respective peroxyl radicals, resulting from O2 trapping, add to 5′-adjacent nucleobases, with a preference for dG. Distal dG's are also oxidatively damaged by the peroxyl radicals. Experiments using a variety of sequences indicate that distal damage occurs via covalent modification of the 5′-adjacent dG, but there is no evidence for electron transfer by the nucleobase peroxyl radicals. © 2014 American Chemical Society.