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Title page for ETD etd-03252016-113945

Type of Document Master's Thesis
Author Bowen, Ryan Scott
URN etd-03252016-113945
Title Structural Studies of N6-(Deoxy-D-Erythro-Pentofuranosyl)-2,6-Diamino-3,4-Dihydro-4-Oxo-5-N-Methylformamido-Pyrimidine and 8-(Deoxyguanosin-N2-yl)-1-Aminopyrene
Degree Master of Science
Department Chemistry
Advisory Committee
Advisor Name Title
Michael P. Stone Committee Chair
Carmelo J. Rizzo Committee Member
  • fapy
  • aminopyrene
  • nuclear magnetic resonance
  • mefapy
  • nuclear magnetic resonance spectroscopy
  • solution structures
  • NMR
  • structural studies
Date of Defense 2016-03-14
Availability unrestricted
N6-(Deoxy-D-Erythro-Pentofuranosyl)-2,6-Diamino-3,4-Dihydro-4-Oxo-5-N-Methylformamido-Pyrimidine (MeFapy-dG) is a deoxyribonucleic acid lesion that has been hypothesized to be induced by methylating chemotherapeutic agents. MeFapy-dG is known to block DNA replication, ultimately leading to a diverse mutagenic profile dependent on the sequence context. 8-(Deoxyguanosin-N2-yl)-1-Aminopyrene (N2-AP-dG) is a bulky DNA adduct that is a product of 1-nitropyrene (1-NP) nitroreduction. 1-NP is a prevalent chemical carcinogen found in diesel exhaust, coal fly ash, and other environmental pollutants. Previous research demonstrated that N2-AP-dG stalls replication with Dpo4 with the potential to induce various mutations. Both MeFapy-dG and N2-AP-dG were studied in the structural context using Nuclear Magnetic Resonance Spectroscopy (NMR). In the case of MeFapy-dG, important cross-peaks were located in the NMR spectra providing structural evidence of the ?- and ?-anomers, indicating that both populations were present in solution. Furthermore, the N2-AP-dG unmodified duplex was characterized, demonstrating that the unmodified sequence context adopted normal B-type DNA. The modified N2-AP-dG NMR spectra provided evidence that the adduct was oriented in the minor groove of the DNA duplex, pointing in the 3’ direction of the modified strand, with minimal perturbation of the global DNA structure.
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