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

有了这笔少数民族研究计划补助金，布莱恩特-弗里德里希教授将获得与氧化核酸损伤领域相关的知识和诀窍。她还将开发合成修饰核苷和核苷酸的方法，这些核苷和核苷酸在寡核苷酸系统中起到C-3‘-自由基前体的作用。通过参加几个关于辐射对DNA的损害和衰老生物学的会议，将为拟议的研究奠定基础。这些会议将汇集该领域具有化学、物理、生物和医学专业知识的从业者。这将允许与不仅研究DNA损伤机制而且研究实际诱导过程、DNA损伤的性质、结构和分布以及细胞效应和修复过程的美国和外国研究人员进行互动。上述相互作用将被用作背景信息，以建立一个研究计划，重点是使用合成有机、物理有机和生物有机技术来独立生成核苷自由基，并鉴定这些自由基物种的降解产物。合成含有多种天然碱基和修饰碱基的前体是必要的。这些经过修饰的衍生物将用于单体实验，以确定有效产生所需自由基所需的条件，重点是反应时间、溶剂、适当的衍生物等。当这些细节确定后，将对单体进行进一步的修饰，以促进它们在自动DNA合成中的使用。Amanda Bryant-Friedrich教授在题为“C-3‘-核酸自由基：生成和机理研究”的提案中提出的工作受到热烈支持。

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.