Title:
Charge migration and one-electron oxidation at adenine and thymidine containing DNA strands and role of guanine N1 imino proton in long range charge migration through DNA

dc.contributor.advisor Schuster, Gary B.
dc.contributor.author Ghosh, Avik Kumar en_US
dc.contributor.committeeMember Bunz, Uwe
dc.contributor.committeeMember Doyle, Donald
dc.contributor.committeeMember Fahrni, Christoph
dc.contributor.committeeMember Wartell, Roger
dc.contributor.department Chemistry and Biochemistry en_US
dc.date.accessioned 2007-08-16T17:43:59Z
dc.date.available 2007-08-16T17:43:59Z
dc.date.issued 2007-05-16 en_US
dc.description.abstract DNA is the carrier of biological information and damage to DNA has been believed to be responsible for many diseases including aging and cancer. One electron oxidation by charge migration through DNA is one of the processes that lead to DNA damage. It is known that the guanine N1 imino proton can be transferred to the N3 of cytidine that is hydrogen bonded to it. Some reports have implication that this proton transfer and radical cation migration are coupled to each other. We have incorporated 5-fluoro-2 -deoxycytidine (F5dC) in place of normal dC in DNA duplexes. Although, the lower pKa of F5dC should perturb the proton transfer process from the guanine to it, we do not see any change in the charge migration ability compared to the strands having normal cytidines. However, there is a considerable decrease in the guanine damage, when there is F5dC opposite to it. These results indicate that the charge migration is not coupled with proton transfer process, but the change in basicity affects the reactivity of the guanine radical cation. We have also reported a systematic study on the charge migration through adenine (A) and thymidine (T) containing DNA strands. The damage has predominantly seen in thymidine, although from oxidation potentials reaction at adenine was expected. The thymidine reaction has been analyzed thoroughly. It has similar distance dependence property as the well known guanine damage. Study of thymidine damage in presence of radical scavengers, replacement of thymidines by Uracil and HPLC-MS study point toward reactions involving tandem lesion. On the basis of these information and molecular modeling study we have proposed a possible pathway leading to one-electron oxidation at the thymidines. en_US
dc.description.degree Ph.D. en_US
dc.identifier.uri http://hdl.handle.net/1853/16203
dc.publisher Georgia Institute of Technology en_US
dc.subject DNA en_US
dc.subject Charge migration en_US
dc.subject Oxidative damage en_US
dc.title Charge migration and one-electron oxidation at adenine and thymidine containing DNA strands and role of guanine N1 imino proton in long range charge migration through DNA 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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