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Date of Award

2018

Document Type

Restricted Thesis: Campus only access

Degree Name

Bachelor of Science

Abstract

When 2’-deoxyguanosine is exposed to reactive oxygen species, 8-oxo-2’-deoxyguanosine (OdG) can result. OdG can form stable base pairs to both 2’-deoxycytidine (dC) and to 2’-deoxyadenosine (dA), causing polymerases to have difficulty discriminating between OdG:dC and OdG:dA base pairs. Previous research has shown that when the 5’-triphosphate analogue of OdG (OdGTP) is incorporated opposite dA, a dAàdC transversion can occur. This alternate base pairing is a possible explanation of why OdG has been linked to ageing, Alzheimer’s, and cancer. Biochemical experiments with analogs of OdG may be useful for better understanding how various sites on OdG affect its interaction with different polymerases and, thus, OdG mutagenicity. To this end, the Hamm lab synthesizes nucleotide analogues on the spectrum between dG and OdG, including 8-bromo-2’-deoxyinosine (BrdI), 8-oxo-2’-deoxyinosine (OdI), and 8-thio-2’-deoxyinosine (SdI). To better understand the incorporation of OdGTP, the 5’-triphosphate derivatives of BrdI, OdI, and SdI were synthesized. NMR studies were performed in order to confirm the structures of the triphosphates as well as to help determine the purity.

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