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

这项研究计划解决了氧化损伤的核苷，8-氧代-2 '-脱氧鸟苷（OdG）的诱变和修复，这是最突出的DNA损伤之一，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/或电子性质，将合成dG和OdG之间的光谱上的类似物。比较各种聚合酶和DNA修复酶与dG、OdG及其类似物的活性将分离导致OdG生物活性的确切因素。这些研究也将被用来作为一种机制，以更好地连接化学和生物学在课堂上。在有机化学和非专业课程的学生将看到真实的世界的应用，而生物化学的学生将获得生物分子和代谢的化学理解。在有机和高分子化学计划的支持下，里士满大学化学系的Michelle哈姆教授，正在发展对决定细胞中化合物生物活性的特定性质和相互作用的理解。哈姆教授的研究针对与衰老和各种疾病有关的特定DNA损伤。通过各种合成和生物化学研究，将更好地了解突变和DNA修复的化学性质。通过在本科化学课程中引入生物和生物化学主题，哈姆教授正在帮助学生建立化学和生物学之间的联系，并欣赏这些科学的现实意义。

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.