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Advancement of Nucleic Acid X-Ray Crystallography for Structure

Nucleic acid, including both DNA and RNA, plays a most important role in living organisms. To understand how nucleic acid behaves in vitro and in vivo is essential for creating drugs that will inhibit nucleic acids and their complexes with proteins, and for understanding the molecular mechanisms of DNA and RNA molecules. In his research, Zhen Huang, Assistant Professor of Biochemistry and Chemistry at The Graduate Center and Brooklyn College, integrates chemical synthetic skills, enzymatic methods, and molecular biology techniques to better understand structural properties and molecular mechanisms of these types of macromolecules. Current projects are related to synthesis of analogs of nucleosides and nucleotides, derivatization of nucleic acids for DNA and RNA X-ray crystal structure studies, in vitro and in vivo selection and evolution of ligand-binding and catalytic RNAs, ribozyme gene therapy, and direct quantitation of gene expression.

In his research, funded by the National Institute of Health (NIH), CUNY Collaborative grant, CUNY Groundwork grant, as well as grants provided by New Dimension Research Inc., Glen Research Inc., and Dharmacon Research Inc., Professor Huang has successfully demonstrated a novel derivatization strategy using selenium to replace nucleotide oxygen atoms. The selenium atoms do not disrupt the structure and function of the macromolecules, thus making it ideal atoms for structure determination in drug design. This novel technology can also be used in crystal structure studies of nucleic acid-protein complexes by derivatizing nucleic acids instead of the protein counterparts. Additional work involves these techniques to study ribozyme molecules, which are a class of recently-discovered catalysts in biochemistry that scientists believe will one day be important in treating diseases with gene therapy. The preliminary findings of his work have been published in the Journal of the American Chemical Society and many other research journals.

http://academic.brooklyn.cuny.edu/chem/zhuang/index.htm