New Paradigm of Nucleic Acids Engineered with Selenium

在国家科学基金会有机和高分子化学项目的支持下，格鲁吉亚州立大学化学系的黄震教授将继续他的工作，通过原子特异性取代氧将硒掺入DNA和RNA，这将导致发现核酸的新性质，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硒对氧的替代作用，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，当用硒取代DNA中胸苷的4-氧时，令人惊讶地发现，通常不可见的DNA变得可见（黄色）。可见DNA的发现，为基于核酸的人类疾病和病原体检测开辟了一条新的途径。此外，该项目将通过硒核酸（SeNA）的基础研究提供对核酸性质的新见解。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。已经观察到Se-DNA对UV诱导的损伤具有抗性，并且Se-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。黄教授将继续秉承格鲁吉亚州立大学化学系的优良传统，为本科生和研究生提供教育和服务，包括少数族裔学生。这个项目和相关的研究活动是培训学生的一个很好的工具。这项研究需要多个学科的整合，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，该项目将产生协同作用，在格鲁吉亚州立大学的化学和生物系的研究培训。

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.