title: Synthesis of C3' modified nucleosides for selective generation of the C3'-deoxy-3'-thymidinyl radical: a proposed intermediate in LEE induced DNA damage.
abstract: DNA damage pathways induced by low-energy electrons (LEEs) are believed to involve the formation of 2-deoxyribose radicals. These radicals, formed at the C3' and C5' positions of nucleotides, are the result of cleavage of the C-O phosphodiester bond through transfer of LEEs to the phosphate group of DNA oligomers from the nucleobases. A considerable amount of information has been obtained to illuminate the identity of the unmodified oligonucleotide products formed through this process. There exists, however, a paucity of information as to the nature of the modified lesions formed from degradation of these sugar radicals. To determine the identity of the damage products formed via the 2',3'-dideoxy-C3'-thymidinyl radical (C3'(dephos) sugar radical), phenyl selenide and acyl modified sugar and nucleoside derivatives have been synthesized, and their suitability as photochemical precursors of the radical of interest has been evaluated. Upon photochemical activation of C3'-derivatized nucleosides in the presence of the hydrogen atom donor tributyltin hydride, 2',3'-dideoxythymidine is formed indicating the selective generation of the C3'(dephos) sugar radical. These precursors will make the identification and quantification of products of DNA damage derived from radicals generated by LEEs possible.
authors.affiliation: Department of Medicinal and Biological Chemistry, The University of Toledo, 2801 W. Bancroft Street, Toledo, Ohio 43606, USA.
authors.forename: Suaad A S
authors.initials: SA
authors.lastname: Audat
authors.forename: CherylAnn Trzasko
authors.initials: CT
authors.lastname: Love
authors.forename: Buthina A S
authors.initials: BA
authors.lastname: Al-Oudat
authors.forename: Amanda C
authors.initials: AC
authors.lastname: Bryant-Friedrich
mesh_terms: D002244:Carbon / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D004249:DNA Damage; D003855:Deoxyribose / Q000737:chemistry*; D015224:Dideoxynucleosides / Q000737:chemistry*; D004578:Electron Spin Resonance Spectroscopy; D004583:Electrons; D005609:Free Radicals / Q000737:chemistry; D008027:Light; D008958:Models, Molecular; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry*; D009711:Nucleotides / Q000138:chemical synthesis* / Q000737:chemistry*; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000737:chemistry*; D010777:Photochemistry; D013056:Spectrophotometry, Ultraviolet
chemical_list: D015224:Dideoxynucleosides; D005609:Free Radicals; D009705:Nucleosides; D009711:Nucleotides; D009841:Oligonucleotides; C019336:2',3'-dideoxythymidine; D003855:Deoxyribose; D002244:Carbon; D004247:DNA