Title:
Investigation of the Role of Groove Hydration and Charged Nucleosides in DNA Charge Transfer

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dc.contributor.advisor Schuster, Gary B.
dc.contributor.author Onyemauwa, Frank Okezie en_US
dc.contributor.committeeMember Doyle, Donald
dc.contributor.committeeMember Fahrni, Christoph
dc.contributor.committeeMember Gelbaum, Leslie
dc.contributor.committeeMember Landman, Uzi
dc.contributor.department Chemistry and Biochemistry en_US
dc.date.accessioned 2006-09-01T19:43:57Z
dc.date.available 2006-09-01T19:43:57Z
dc.date.issued 2006-08-11 en_US
dc.description.abstract Structural 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.description.degree Ph.D. en_US
dc.format.extent 3898954 bytes
dc.format.mimetype application/pdf
dc.identifier.uri http://hdl.handle.net/1853/11634
dc.language.iso en_US
dc.publisher Georgia Institute of Technology en_US
dc.subject DNA oxidation en_US
dc.subject Synthesis of pyridinium nucleoside
dc.subject Charged nucleosides
dc.subject DNA charge transfer
dc.subject.lcsh Nucleosides en_US
dc.subject.lcsh Nucleosynthesis en_US
dc.subject.lcsh DNA Synthesis en_US
dc.title Investigation of the Role of Groove Hydration and Charged Nucleosides in DNA Charge Transfer en_US
dc.type Text
dc.type.genre Dissertation
dspace.entity.type Publication
local.contributor.advisor Schuster, Gary B.
local.contributor.corporatename School of Chemistry and Biochemistry
local.contributor.corporatename College of Sciences
relation.isAdvisorOfPublication 5496b90a-0188-49d8-9ec7-fa1ee916e66e
relation.isOrgUnitOfPublication f1725b93-3ab8-4c47-a4c3-3596c03d6f1e
relation.isOrgUnitOfPublication 85042be6-2d68-4e07-b384-e1f908fae48a
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