CAREER: C-3'-Nucleic Acid Radicals: Generation and Mechanistic Investigations

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Oxidative processes are at the heart of numerous chemical and biochemical processes, including the damage of nucleic acids by ionizing radiation or specific drug interactions. This project involves the synthesis of modified nucleosides and nucleotides that will permit the elucidation of the mechanism of degradation of C-3' nucleotide radicals in DNA and RNA. Modifed nucleosides containing photoactive functional groups will be synthesized and incorporated into small DNAs and RNAs designed for the investigation of damage events. The nature and fate of nucleoside radicals derived from these site-specifically functionalized nucleic acid systems will be explored by a variety of chemical, analytical, and biophysical methods. A curriculum for a Master of Science degree will be developed, targeting specific groups in an effort to increase the pool of underrepresented minorities in the chemical workforce. This program specifically targets students who are ill prepared for graduate studies or who have not been successful in previous attempts to receive a graduate degree due to a lack of proper preparation.With the support of this CAREER Award from the Organic and Macromolecular Chemistry Program, Professor Amanda Bryant-Friedrich, of the Department of Chemistry at Oakland University, is developing an understanding of the chemical processes which result in the damage of DNA and RNA. Radiation, drug interactions, and other oxidative processes can lead to the formation of nucleic acid radicals. Through the synthesis and manipulation of modified nucleic acid subunits, Professor Bryant-Friedrich is elucidating the mechanisms by which these radicals lead to nucleic acid degradation. Professor Bryant-Friedrich is also working toward increasing the representation of women and minorities in the chemical workforce. Through development of a Master of Science program at Oakland University, Professor Bryant-Friedrich will provide a program targeting students who are academically ill-prepared for graduate study, placing them on track for employment or for placement in competitive doctoral programs.