CAREER: Chemical Investigations into the Bioactivity of the Damaged DNA Nucleotide 8-Oxo-2'-deoxyguanosine

职业：对受损 DNA 核苷酸 8-Oxo-2-脱氧鸟苷生物活性的化学研究

• 批准号: 0239664
• 负责人: Michelle Hamm
• 金额: $ 40.43万
• 依托单位: University of Richmond
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-02-01 至 2009-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0239664&HistoricalAwards=false
• 关键词: CAREER; Chemical; Investigations; into; Bioactivity

This research program addresses the mutagenesis and repair of the oxidatively damaged nucleoside, 8-oxo-2'-deoxyguanosine (OdG), one of the most prominent DNA lesions and linked to aging and several diseases. In order to probe the steric and/or electronic properties that dictate the bioactivity of OdG, analogs on the spectrum between dG and OdG will be synthesized. Comparisons of the activity of various polymerases and DNA repair enzymes with dG, OdG, and their analogs will isolate the exact factors leading to the bioactivity of OdG. These studies will also be used as a mechanism to better connect chemistry to biology in the classroom. Students in organic chemistry and a non-majors course will see real world applications, while biochemistry students will gain a chemical understanding of biomolecules and metabolism.With the support of this CAREER Award from the Organic and Macromolecular Chemistry Program, Professor Michelle Hamm, of the Department of Chemistry at the University of Richmond, is developing an understanding of the specific properties and interactions that dictate the bioactivity of chemical compounds in cells. Professor Hamm's studies target particular DNA lesions that have been linked to aging and various diseases. Through a variety of synthetic and biochemical studies, a better understanding of the chemical nature of mutation and DNA repair will be obtained. Through the introduction of biological and biochemical themes throughout the undergraduate chemistry curriculum, Professor Hamm is helping students make the connection between chemistry and biology and to appreciate the real-world implications of these sciences.

该研究计划介绍了氧化受损的核苷，8-oxo-2'-脱氧鸟苷（ODG）的诱变和修复，这是最突出的DNA病变之一，与衰老和几种疾病有关。为了探测决定ODG生物活性的空间和/或电子特性，将合成DG和ODG之间光谱上的类似物。与DG，ODG及其类似物的各种聚合酶和DNA修复酶的活性的比较将隔离导致ODG生物活性的确切因素。这些研究还将用作更好地将化学与教室生物学联系起来的机制。有机化学和非裁判课程的学生将看到现实世界的应用，而生物化学的学生将对生物分子和代谢进行化学理解。在有机和大​​分子化学计划中获得了这一职业奖，有机和巨型分子化学计划，里奇蒙德大学化学学院的化学性化学性化学和互动性的互动性和互动性相互作用的米歇尔·哈姆（Michelle Hamm）教授米歇尔·哈姆（Michelle Hamm）教授。 HAMM教授的研究针对与衰老和各种疾病有关的特定DNA病变。通过各种合成和生化研究，将获得对突变和DNA修复的化学性质的更好理解。通过在整个本科化学课程中引入生物学和生物化学主题，Hamm教授正在帮助学生建立化学与生物学之间的联系，并欣赏这些科学的现实含义。