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.

在美国国家科学基金会有机和大分子化学项目的支持下，乔治亚州立大学化学系的黄振教授将继续他的工作，通过原子特异性取代氧将硒结合到dna和rna中，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，本项目将重点研究用硒代替氧，硒为DNA和RNA提供了许多有用和独特的性质，并创造了核酸的新范式。例如，当用硒代替DNA中的胸腺嘧啶的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）。单原子工程对可见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，本项目将通过对硒-核酸（SeNA）的基础研究，为核酸性质的研究提供新的见解。该化学发生研究将探索硒核酸的新化学、碱基配对和堆叠相互作用、物理化学和生物化学。已经观察到，硒DNA对紫外线诱导的损伤具有抗性，并且硒核碱基衍生的DNA具有与相应的天然DNA几乎相同的x射线晶体结构。新的化学和酶合成这些新的硒磷酰胺，三磷酸硒和硒核酸也将被开发。凭借这一职业奖，黄教授将延续乔治亚州立大学化学系在教育和服务本科生和研究生（包括少数族裔学生）方面的强大传统。这个项目和相关的研究活动是训练学生的一个很好的工具。本研究需要有机合成、核酸化学、动力学、热力学、生物化学、生物物理化学、结构生物学等多学科的整合；因此，该项目将在乔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。