With this Minority Research Planning Grant Professor Bryant-Friedrich will gain knowledge and know-how related to the field of oxidative nucleic acid damage. She will also develop methodologies for the synthesis of modified nucleosides and nucleotides that function as C-3'-radical precursors in oligonucleotide systems. A foundation for the proposed research will be built by attending several conferences on radiation damage to DNA and on the biology of aging. These conferences will bring together practitioners in the field with expertise in chemistry, physics, biology and medicine. This will allow interaction with US and foreign researchers who investigate not only the mechanism of DNA damage but also those who study the actual induction process, the nature, structure, and distribution of DNA damage, as well as cellular effects and repair processes. The above interactions will be used as background information to establish a research program which focuses on the use of synthetic organic, physical organic, ahd bioorganic techniques for the independent generation of nucleoside radicals and the identification of the products that result from the degradation of these radical species. It will be necessary to synthesize precursors containing a wide variety of naturally occurring nucleobases as well as modified bases. These modified derivatives will be used in monomer experiments to determine the conditions necessary for efficient generation of the desired radicals, focusing on reaction times, solvents, proper derivatives, etc. When these details are established, further modification of the monomers will be carried out to facilitate their use in automated DNA synthesis. The work proposed by Professor Amanda Bryant-Friedrich in her proposal entitled "C-3'-Nucleic Acid Radicals: Generation and Mechanistic Investigations" is enthusiastically supported.
