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

有了这个少数民族研究规划补助金教授布莱恩特-弗里德里希将获得相关的知识和专业知识的氧化核酸损伤的领域。她还将开发用于合成修饰核苷和核苷酸的方法，这些修饰核苷和核苷酸在寡核苷酸系统中充当C-3 '-自由基前体。这项研究的基础将通过参加几次关于DNA辐射损伤和衰老生物学的会议来建立。这些会议将汇集在化学，物理学，生物学和医学领域的专业知识的从业人员。这将允许与美国和外国研究人员进行互动，这些研究人员不仅研究DNA损伤的机制，还研究DNA损伤的实际诱导过程、性质、结构和分布，以及细胞效应和修复过程。上述相互作用将被用作背景信息，以建立一个研究计划，该计划侧重于使用合成有机，物理有机，和生物有机技术，用于核苷自由基的独立产生和这些自由基物种降解的产物的鉴定。有必要合成含有各种天然存在的核碱基以及修饰碱基的前体。这些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修饰，以促进它们在自动化DNA合成中的使用。阿曼达·布莱恩特-弗里德里希教授在她题为“C-3 '-核酸自由基：生成和机理研究”的提案中提出的工作得到了热烈支持。

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.