Redox Photochemistry of Oxidized Bases in DNA and RNA

DNA 和 RNA 中氧化碱基的氧化还原光化学

• 批准号: 1152533
• 负责人: Cynthia Burrows
• 金额: $ 48.8万
• 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: 2012
• 资助国家: 美国
• 起止时间: 2012-04-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1152533&HistoricalAwards=false
• 关键词: Redox; Photochemistry; Oxidized; Bases; DNA

With this award, the Chemistry of Life Processes Program is supporting the research of Professor Cynthia Burrows of the University of Utah. Professor Burrows hypothesizes that simple chemical transformations of RNA bases could have been the key steps in creating redox active catalysts driving early chemical systems toward a primitive metabolism. With prior NSF funding, her laboratory has shown that the oxidized base 8-oxoguanine serves as a photochemical catalyst to reductively reverse cyclobutane pyrimidine dimers to monomers. In this reaction, 8-oxoguanine acts as a flavin mimic to facilitate excited state electron transfer. Future work will explore 8-oxopurines and other redox active RNA purine and pyrimidine base derivatives for their ability to mediate oxidation and reduction reactions. For example, key reactions of early Earth must have included the ability to interconvert alcohols and aldehydes or ketones (e.g. lactate/pyruvate) using redox cofactors analogous to NADH and FADH2. Reactions such as these will be studied in RNA world-like conditions in order to test the hypothesis that simpler versions of these RNA-based cofactors could have presaged modern-day metabolism.The broader impacts of this project are demonstrated in the unusual link between DNA damage and repair chemistry pertinent to cancer and the chemistry of primordial Earth. Photoinduced electron transfer appears to play a role in both realms, and insights from this work could be broadly applicable to other disciplines. Students trained on the project will be involved in interdisciplinary sciences including aspects of synthetic and physical organic, analytical and biochemistry. Professor Burrows has demonstrated continuing leadership in broadening participation, including programs that advance the careers of women scientists, and will continue to be active in dissemination of research to public audiences.

生命过程化学项目通过该奖项支持犹他大学辛西娅·伯罗斯教授的研究。 Burrows 教授假设，RNA 碱基的简单化学转化可能是创造氧化还原活性催化剂、推动早期化学系统走向原始新陈代谢的关键步骤。 在之前 NSF 的资助下，她的实验室已证明氧化碱基 8-氧代鸟嘌呤可作为光化学催化剂，将环丁烷嘧啶二聚体还原逆转为单体。 在此反应中，8-氧代鸟嘌呤充当黄素模拟物，促进激发态电子转移。 未来的工作将探索 8-氧代嘌呤和其他氧化还原活性 RNA 嘌呤和嘧啶碱衍生物介导氧化和还原反应的能力。 例如，早期地球的关键反应必须包括使用类似于 NADH 和 FADH2 的氧化还原辅因子相互转化醇和醛或酮（例如乳酸盐/丙酮酸盐）的能力。 诸如此类的反应将在类似 RNA 世界的条件下进行研究，以检验这些基于 RNA 的辅因子的简单版本可能预示着现代新陈代谢的假设。DNA 之间不寻常的联系证明了该项目的更广泛影响与癌症相关的损伤和修复化学以及原始地球的化学。 光诱导电子转移似乎在这两个领域都发挥着作用，这项工作的见解可以广泛适用于其他学科。 接受该项目培训的学生将涉及跨学科科学，包括合成和物理有机、分析和生物化学方面。 伯罗斯教授在扩大参与方面表现出持续的领导力，包括促进女科学家职业发展的计划，并将继续积极向公众传播研究成果。