Evidence for glycosidic bond rotation in a nucleobase peroxyl radical and its effect on tandem lesion formation.
Nucleobase peroxyl radicals are the major reactive intermediates formed in DNA when the biopolymer is exposed to gamma-radiolysis under aerobic conditions. The major reaction pathways for the peroxyl radical (1) derived from 5,6-dihydro-2'-deoxyuridin-6-yl involve pi-bond addition to or hydrogen atom abstraction from the adjacent nucleotides to produce tandem lesions. The ability to independently generate 1 at a defined site in DNA enabled us to probe its reactivity by varying the local DNA structure. The effect of DNA structure variation reveals that 1 reacts from its syn- and anti-conformations in competition with trapping by thiol. These experiments also reveal that tandem lesions will be produced as a mixture of diastereomers, which could impact their biological effects.
Hong
In Seok
IS
Department of Chemistry, Johns Hopkins University, 3400 N. Charles St., Baltimore, Maryland 21218, USA.
Carter
K Nolan
KN
Greenberg
Marc M
MM
D004247:DNA / Q000737:chemistry* / Q000528:radiation effects; D004249:DNA Damage; D005609:Free Radicals / Q000737:chemistry* / Q000528:radiation effects; D006027:Glycosides / Q000737:chemistry* / Q000528:radiation effects; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009705:Nucleosides / Q000737:chemistry* / Q000528:radiation effects*; D011675:Pulse Radiolysis; D013237:Stereoisomerism
D005609:Free Radicals; D006027:Glycosides; D009705:Nucleosides; D004247:DNA