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.

这项研究计划研究氧化损伤的核苷8-氧-2‘-脱氧鸟苷(ODG)的突变和修复，ODG是最突出的DNA损伤之一，与衰老和几种疾病有关。为了探索决定ODG生物活性的空间和/或电子性质，将在DG和ODG之间合成类似物。将各种聚合酶和DNA修复酶的活性与DG、ODG及其类似物进行比较，将分离出导致ODG生物活性的确切因素。这些研究还将被用作一种机制，在课堂上更好地将化学与生物联系起来。有机化学和非专业课程的学生将看到现实世界的应用，而生物化学学生将获得对生物分子和新陈代谢的化学理解。在有机和高分子化学项目的这一职业奖的支持下，里士满大学化学系的米歇尔·哈姆教授正在发展对决定细胞中化合物生物活性的特殊性质和相互作用的理解。哈姆教授的研究针对的是与衰老和各种疾病有关的特定DNA损伤。通过各种合成和生化研究，将对突变和DNA修复的化学本质有更好的了解。通过在本科化学课程中引入生物和生化主题，哈姆教授正在帮助学生在化学和生物之间建立联系，并欣赏这些科学的现实含义。