Date of Graduation
Master of Science in Chemistry
deoxyribonucleic acid, base excision repair, ethenodeoxyadenosine, abasic, deuterium, solid-state nuclear magnetic resonance
DNA-protein interactions are an increasingly important area of study in order to understand the true recognition mechanism in which DNA repair is allowed to take place. The structure and dynamics of the DNA backbone could provide information about the energy barriers that the protein must overcome to facilitate repair. Several deuterated monomers have been synthesized for incorporation into DNA and characterization using solid state NMR and Raman scattering. The monomers include 2''-2H-deoxyadenosine, 3'-2H-thymidine, 5'-2H-deoxyadenosine and 5'-2H-deoxyuridine. The synthesis procedures utilized are standard published protocols that have been applied to deoxynucleoside lesions. The successful reactions for 3'-2H-thymidine lead to transforming the nucleoside into a phosphoramidite and incorporating it into known DNA sequences, the Dickerson dodecomer ds(5'-CGCGAATTCGCG'3'). Three sequences were made; control sequence; sequence containing an ethenoadenine site at the 5 position; and sequence containing an abasic site at the 5 position. All sequences had the labeled thymidine at the 8 position, opposite the lesion. Solid state NMR was performed on these samples through comparative studies. The data showed major differences between the natural DNA and the DNA containing base lesions. This indicates that there are alterations in the dynamics at the deuterium labeled sites within the DNA sequences studied.
© Melissa Nicole Hayes
Hayes, Melissa Nicole, "Deuterium Solid State Nuclear Magnetic Resonance of DNA Containing Single Base Lesions" (2012). MSU Graduate Theses. 1979.