Systematic derivatization of nucleotides and nucleic acids with selenium for X-ray crystallography

ORGN 681

Zhen Huang, Huang@gsu.edu, Jozef Salon, chejxf@langate.gsu.edu, Gary E. Brandt, gbrandt1@student.gsu.edu, Julianne Caton-Williams, jcwill_tt@yahoo.com, and Jia Sheng, jsheng1@student.gsu.edu. Department of Chemistry, Georgia State University, 38 Peachtree Center Avenue, Atlanta, GA 30303-3083
X-ray crystallography is a powerful tool for high-resolution structure determination of nucleic acids and their complexes with proteins. Derivatization with heavy atoms for phase determination, a long-standing problem in X-ray crystallography, however, has largely slowed down structural determination of nucleic acids, especially functional RNAs, with novel folds. To solve this problem, we recently initiated systematic syntheses of RNAs and DNAs modified with selenium for X-ray crystallography, by site-specifically replacing oxygen. We will present the current chemical synthesis and enzymatic incorporation of RNAs and DNAs containing Se-modifications at a variety of positions, present activity study of the Se-derivatized ribozymes, and present the structural study of the Se-modified DNAs and RNAs. This strategy of RNA and DNA derivatization with selenium has great potential as a general methodology in X-ray crystallography. This novel strategy will significantly facilitate nucleic acid X-ray crystallography and structural study of nucleic acid-protein complexes.

 

Lipids, Nucleotides, and Mimetics
1:00 PM-4:20 PM, Thursday, 30 March 2006 Georgia World Congress Center -- C301, Oral

Division of Organic Chemistry

The 231st ACS National Meeting, Atlanta, GA, March 26-30, 2006