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5,6-Dihydropyrimidine Peroxyl Radical Reactivity in DNA

[Image: see text] 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 oligonucl...

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Detalles Bibliográficos
Autores principales: San Pedro, Joanna Maria N., Greenberg, Marc M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2014
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3980663/
https://www.ncbi.nlm.nih.gov/pubmed/24579910
http://dx.doi.org/10.1021/ja412562p
Descripción
Sumario:[Image: see text] 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 O(2) 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.