Mechanisms of Nucleic Acid Oxidation and Cross-linking

核酸氧化和交联的机制

• 批准号: 0514612
• 负责人: Cynthia Burrows
• 金额: $ 47.5万
• 依托单位: University of Utah
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0514612&HistoricalAwards=false
• 关键词: Mechanisms; Nucleic; Acid; Oxidation; Cross

The Organic and Macromolecular Chemistry Program supports Professor Cynthia J. Burrows at the University of Utah who proposes to explore mechanistically how DNA-protein crosslinks arise during the course of oxidative damage. Oxidative insult to chromatin leading to formation of DNA-protein crosslinks is poorly understood at the molecular level. Studies outlined in the proposal build on recent results showing that 8-oxo-7, 8-dihydroguanosine is sensitive to further oxidation by one-electron oxidants leading to a quinonoid intermediate that is nucleophilically trapped to ultimately generate hydantoin products. Methods will be developed to understand the chemical structures responsible for DNA-protein crosslinking via both DNA oxidation and protein oxidation. Professor Burrows hopes to formulate a detailed molecular picture of how DNA is oxidized in the presence of reactive species such as protein and polyamine nucleophiles.The Organic and Macromolecular Chemistry Program supports Professor Cynthia J. Burrows who will train undergraduate, graduate, and postdoctoral students to be well versed in mechanistic organic chemistry. These students will also gain biotechnical skills in the manipulation of nucleic acids and proteins and contribute to our molecular understanding of DNA damage, which underlies processes leading to aging, cancer, and neurological disorders. In addition, Professor Burrows' laboratory will continue to serve as a resource to faculty members at 4-year institutions to collaborate on projects in nucleic acid chemistry and to provide mass spectrometry expertise to assist these collaborations.

有机和大分子化学计划支持犹他大学的Cynthia J. Burrows教授，他建议在氧化损伤过程中从机械上探索DNA-蛋白交联是如何出现的。对染色质的氧化侮辱会导致形成DNA-蛋白交联的形成在分子水平上鲜为人知。该提案中概述的研究基于最新结果，表明8-氧，8-二氢瓜氨糖苷对一单电子氧化剂的进一步氧化敏感，从而导致甲核酸中间体被核细胞捕获至最终产生羟to蛋白产物。将开发方法来理解负责通过DNA氧化和蛋白质氧化的DNA蛋白交联的化学结构。 Burrows教授希望制定一个详细的分子图片，即在存在反应性物种（例如蛋白质和多胺接亲核剂）的情况下如何将DNA氧化。精通机械有机化学。这些学生还将在操纵核酸和蛋白质方面获得生物技术技能，并有助于我们对DNA损伤的分子理解，这是导致衰老，癌症和神经系统疾病的过程的基础。此外，Burrows教授的实验室将继续为4年机构的教职员工提供有关核酸化学项目合作的资源，并提供质谱专业知识以协助这些合作。