New Paradigm of Nucleic Acids Engineered with Selenium

用硒设计的核酸的新范例

• 批准号: 0750235
• 负责人: Zhen Huang
• 金额: $ 35.4万
• 依托单位: Georgia State University Research Foundation, Inc.
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-15 至 2011-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0750235&HistoricalAwards=false
• 关键词: New; Paradigm; Nucleic; Acids; Engineered

With support from the Organic and Macromolecular Chemistry Program at the National Science Foundation for this new award, Professor Zhen Huang, of the Department of Chemistry at Georgia State University, will continue his work on the selenium incorporation into DNAs and RNAs by atom-specific substitution of oxygen, which will lead to discovering novel properties, novel materials, and applications for nucleic acids. Since oxygen and selenium are in the same elemental family, this project will focus on oxygen replacement with selenium, which provides DNA and RNA with many useful and unique properties and creates a new paradigm of nucleic acids. For instance, when replacing 4-oxygen of thymidine in DNA with selenium, surprisingly, it was discovered that normally invisible DNA becomes visible (yellow color). The new discovery of the visible DNA, by single atom engineering, opens a novel avenue for nucleic acid-based human disease and pathogen detection. Furthermore, this project will provide new insights into nucleic acid properties through the fundamental study of the selenium-nucleic acid (SeNA). This chemogenetic research will explore novel chemistry, base-pairing and stacking interactions, physical chemistry and biochemistry of selenium-nucleic acids. It has been observed that Se-DNA is resistant to UV-induced damage, and the Se-nucleobase-derivatized DNA has an X-ray crystal structure virtually identical to that of the corresponding native DNA. New chemical and enzymatic syntheses of these novel Se-phosphoramidites, Se-triphosphates and Se-nucleic acids will also be developed.With this CAREER award, Professor Huang will continue the strong tradition of the Chemistry Department at Georgia State University in educating and serving undergraduate and graduate students, including underrepresented minority students. This project and the associated research activity is an excellent vehicle for the training of students. This research requires the integration of multiple disciplines, including organic synthesis, nucleic acid chemistry, kinetics, thermodynamics, biochemistry, biophysical chemistry, and structural biology; therefore, this project will generate synergy in research training in both the Chemistry and Biology Departments at Georgia State University.

在国家科学基金会有机和高分子化学项目对这一新奖项的支持下，佐治亚州立大学化学系的Zhen Huang教授将继续他通过原子特异性取代将硒掺入DNA和RNA的工作氧，这将导致发现核酸的新特性、新材料和应用。由于氧和硒属于同一元素家族，因此该项目将重点研究用硒替代氧，这为 DNA 和 RNA 提供了许多有用且独特的特性，并创建了核酸的新范例。例如，当用硒取代DNA中胸苷的4-氧时，令人惊讶的是，人们发现通常不可见的DNA变得可见（黄色）。通过单原子工程发现的可见 DNA 的新发现，为基于核酸的人类疾病和病原体检测开辟了一条新途径。此外，该项目将通过硒核酸（SeNA）的基础研究为核酸特性提供新的见解。这项化学遗传学研究将探索硒核酸的新化学、碱基配对和堆积相互作用、物理化学和生物化学。据观察，Se-DNA 可抵抗紫外线引起的损伤，并且 Se-核碱基衍生的 DNA 具有与相应天然 DNA 几乎相同的 X 射线晶体结构。还将开发这些新型硒亚磷酰胺、硒三磷酸和硒核酸的新化学和酶法合成方法。凭借这一职业奖，黄教授将延续佐治亚州立大学化学系在教育和服务本科生方面的悠久传统。和研究生，包括代表性不足的少数族裔学生。该项目和相关的研究活动是培训学生的绝佳工具。这项研究需要多学科的整合，包括有机合成、核酸化学、动力学、热力学、生物化学、生物物理化学和结构生物学；因此，该项目将在佐治亚州立大学化学系和生物系的研究培训中产生协同作用。