New Paradigm of Nucleic Acids Engineered with Selenium

Georgia State University Research Foundation, Inc., Atlanta GA

Investigators

Abstract

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.