CAREER: Chemical Investigations into the Bioactivity of the Damaged DNA Nucleotide 8-Oxo-2'-deoxyguanosine

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This research program addresses the mutagenesis and repair of the oxidatively damaged nucleoside, 8-oxo-2'-deoxyguanosine (OdG), one of the most prominent DNA lesions and linked to aging and several diseases. In order to probe the steric and/or electronic properties that dictate the bioactivity of OdG, analogs on the spectrum between dG and OdG will be synthesized. Comparisons of the activity of various polymerases and DNA repair enzymes with dG, OdG, and their analogs will isolate the exact factors leading to the bioactivity of OdG. These studies will also be used as a mechanism to better connect chemistry to biology in the classroom. Students in organic chemistry and a non-majors course will see real world applications, while biochemistry students will gain a chemical understanding of biomolecules and metabolism.With the support of this CAREER Award from the Organic and Macromolecular Chemistry Program, Professor Michelle Hamm, of the Department of Chemistry at the University of Richmond, is developing an understanding of the specific properties and interactions that dictate the bioactivity of chemical compounds in cells. Professor Hamm's studies target particular DNA lesions that have been linked to aging and various diseases. Through a variety of synthetic and biochemical studies, a better understanding of the chemical nature of mutation and DNA repair will be obtained. Through the introduction of biological and biochemical themes throughout the undergraduate chemistry curriculum, Professor Hamm is helping students make the connection between chemistry and biology and to appreciate the real-world implications of these sciences.