RUI: Chemical Investigations into the Bioactivity of the DNA Lesion 8-Oxo-2'-deoxyguanosine

RUI：DNA 损伤 8-Oxo-2-脱氧鸟苷生物活性的化学研究

• 批准号: 0956474
• 负责人: Michelle Hamm
• 金额: $ 17.6万
• 依托单位: University of Richmond
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-01 至 2014-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0956474&HistoricalAwards=false
• 关键词: RUI; Chemical; Investigations; into; Bioactivity

The oxidatively damaged 2'-deoxyguanosine (dG) derivative 8-oxo-2'-deoxyguanosine (OdG) is one of the most prominent DNA lesions and has been linked to ageing as well as several diseases including cancer. Unlike dG which base pairs only with 2'-deoxycytosine (dC) in DNA, OdG can pair with both dC and 2'-deoxyadenosine (dA), thus allowing for mutations during replication. Due to its prominence and promutagenic character, cells have evolved three different repair mechanisms that help lessen the impact of OdG on cells. With the support of this RUI Award from the Chemistry of Life Processes Program, Professor Michelle Hamm of the Department of Chemistry at the University of Richmond will continue her research to better understand the exact steric and/or electronic properties that dictate the bioactivity of OdG. Her lab synthesizes nucleotide analogues on the spectrum between dG and OdG, incorporates them into DNA, and uses them in biochemical experiments focused on the base pairing, replication, and repair of OdG. By comparing the activities of the synthesized analogues to dG and OdG, the exact atomic factors that influence the bioactivity of OdG, and why it differs so strongly from dG, can be isolated. Only by understanding the specific properties and interactions that dictate the activity of a compound can one fully understand its role within the cell. This research will involve undergraduate students at a primarily undergraduate institution and provide training in the synthetic and biochemical techniques used in the proposed studies. The researchers will also learn important skills including time management, critical thinking, experimental design, and verbal and written communication. These activities will prepare them for research in academic or industrial settings, sparking interest in further study at an advanced level.

氧化损伤的2 '-脱氧鸟苷（dG）衍生物8-氧代-2'-脱氧鸟苷（OdG）是最突出的DNA损伤之一，并且与衰老以及包括癌症在内的几种疾病有关。与仅与DNA中的2 '-脱氧胞嘧啶（dC）碱基配对的dG不同，OdG可以与dC和2'-脱氧腺苷（dA）配对，从而允许在复制期间发生突变。由于它的突出和promutagenic字符，细胞已经进化出三种不同的修复机制，有助于减轻OdG对细胞的影响。在生命过程化学项目RUI奖的支持下，里士满大学化学系的Michelle哈姆教授将继续她的研究，以更好地了解决定OdG生物活性的确切空间和/或电子性质。她的实验室在dG和OdG之间的光谱上合成核苷酸类似物，将它们整合到DNA中，并将它们用于生物化学实验，重点是OdG的碱基配对，复制和修复。 通过比较dG和OdG的合成类似物的活性，可以分离出影响OdG生物活性的确切原子因素，以及为什么它与dG如此强烈地不同。只有通过了解决定化合物活性的特定性质和相互作用，才能完全理解其在细胞内的作用。这项研究将涉及本科生在一个主要的本科院校，并提供在拟议的研究中使用的合成和生物化学技术的培训。研究人员还将学习重要的技能，包括时间管理，批判性思维，实验设计以及口头和书面沟通。这些活动将为他们在学术或工业环境中的研究做好准备，激发他们在高级水平上进一步学习的兴趣。