Student Research

Rushina Cholera, Biochemistry and Molecular Biology

Synthesis and Biochemical Characterization of the 8-Oxo-2'-deoxyguanosine Analogue 8-thio-2'-deoxygunosine: Insight into the Bioactivity of a Potent Promutagen

Abstract: 8-Oxo-2'-deoxyguanosine (OdG), a DNA lesion produced during oxidation of 2'-deoxyguanosine (dG), not only contributes to genome mutation, but can also lead to ageing and disease. Consequently, much research has focused on this lesion and its replication by polymerases, repair by glycosylases and base pairing to other nucleotides. Surprisingly, there has been comparatively little study on the exact features that dictate its interaction with these biomolecules. In order to determine the steric and electronic properties that lead to the bioactivity of OdG lesions, we are synthesizing analogues on the spectrum between OdG and dG; one of these is 8-thio-2'-deoxyguanosine (SdG). We have synthesized this nucleoside and incorporated it into 11 nucleotide long oligonucleotides to better understand the base pairing preference of OdG. Melting studies show that that SdG:dC base pairs are less stable than an OdG:dC base pair, consistent with the theory that steric bulk at the C8 position destabilizes dG:dC base pairs. Only by better understanding the exact properties that lead to the bioactivity of OdG can we fully comprehend its overall capacity for promoting mutation and disease.

Presenter	Rushina Cholera
Mentor	Michelle Hamm

Other Research and Publications: (click on links to view)

"Base Pair Stability of 8-Chloro- and 8-lodo-2'-deoxyguanosine Opposite 2'-Deoxycytidine: Implications Regarding the Bioactivity of 8 -Oxo-2'-deoxyguanosine," in Journal of the American Chemical Society v. 127 (2005)

"Oligonucleotide Incorporation of 8-Thio-2'-deoxyguanosine," in Organic Letters v. 6 (2004)