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dc.contributor.authorOnyemauwa, Frank Okezieen_US
dc.date.accessioned2006-09-01T19:43:57Z
dc.date.available2006-09-01T19:43:57Z
dc.date.issued2006-08-11en_US
dc.identifier.urihttp://hdl.handle.net/1853/11634
dc.description.abstractStructural analyses of DNA oligonucleotides indicate the presence of bound water molecules in the major and minor grooves of DNA. These water molecules participate in DNA charge transfer by their reaction with guanosine radical cation to form 7,8-dihydro-8-oxo-guanine (8-oxoG), which when treated with a base leads to DNA strand cleavage. We probed the reaction of guanosine radical cation with water with series of alkyl substituted cytidines and thymidines by incorporating the modified nucleosides into anthraquinone linked DNA duplexes and irradiating them with UV light at 350 nm. The incorporation of these hydrophobic substituents disrupt the DNA spine of hydration, and we have observed that these modifications in the major and minor groove do not effect the trapping or long distance hopping of radical cations in DNA. The second part of the work reported herein examines the role of charged nucleosides in long range charge transfer in duplex DNA. DNA methylation is a naturally occurring process mediated by enzymes responsible for such functions in biological systems. Hypermethylation of DNA can also occur as a result of environmental alkylating agents leading to mutation of the affected cells. Methylation of the ring nitrogen of a purine base can introduce a positive charge in the ring resulting in the cleavage of the glycosidic bond of the nucleoside. To understand the role of a charged nucleoside on charge transfer in DNA, we designed and synthesized cationic nucleoside mimics, which were incorporated into anthraquinone-linked DNA strands and irradiated at 350 nm. The presence of the cationic bases on the duplexes inhibits the migrating hole from hopping along the DNA strand, and induces a prominent local structural distortion of the DNA as a result of the charged nucleobase.en_US
dc.format.extent3898954 bytes
dc.format.mimetypeapplication/pdf
dc.language.isoen_US
dc.publisherGeorgia Institute of Technologyen_US
dc.subjectDNA oxidationen_US
dc.subjectSynthesis of pyridinium nucleoside
dc.subjectCharged nucleosides
dc.subjectDNA charge transfer
dc.subject.lcshNucleosidesen_US
dc.subject.lcshNucleosynthesisen_US
dc.subject.lcshDNA Synthesisen_US
dc.titleInvestigation of the Role of Groove Hydration and Charged Nucleosides in DNA Charge Transferen_US
dc.typeDissertationen_US
dc.description.degreePh.D.en_US
dc.contributor.departmentChemistry and Biochemistryen_US
dc.description.advisorCommittee Chair: Schuster, Gary; Committee Member: Doyle, Donald; Committee Member: Fahrni, Christoph; Committee Member: Gelbaum, Leslie; Committee Member: Landman, Uzien_US


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