Mechanisms of Nucleic Acid Oxidation and Cross-linking

有机和大分子化学项目支持犹他大学的Cynthia J. Burrows教授，她提出探索dna -蛋白质交联在氧化损伤过程中如何产生的机制。对染色质的氧化损伤导致dna -蛋白交联的形成在分子水平上知之甚少。提案中概述的研究基于最近的结果，表明8-氧- 7,8 -二氢鸟苷对单电子氧化剂的进一步氧化很敏感，导致醌类中间体被亲核捕获，最终生成氢妥英产物。方法将开发，以了解化学结构负责通过DNA氧化和蛋白质氧化的DNA-蛋白质交联。巴罗斯教授希望能够详细描述DNA在蛋白质和多胺亲核试剂等活性物质存在下是如何被氧化的。有机和大分子化学项目支持辛西娅J.巴罗斯教授，她将培养本科生、研究生和博士后学生精通机械有机化学。这些学生还将获得操纵核酸和蛋白质的生物技术技能，并有助于我们对DNA损伤的分子理解，DNA损伤是导致衰老、癌症和神经系统疾病的潜在过程。此外，Burrows教授的实验室将继续为四年制院校的教职员工提供资源，以便在核酸化学项目上进行合作，并提供质谱专业知识来协助这些合作。

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.