Synthesis of Se-thymidine phosphoramidites and their incorporation into oligonucleotides for structural and functional study of nucleic acid

ORGN 281

Jia Sheng, jsheng1@student.gsu.edu1, Jozef Salon1, Jiansheng Jiang1, and Zhen Huang, Huang@gsu.edu2. (1) Department of Chemistry, Georgia State University, 38 Peachtree Center Avenue, Atlanta, GA 30303-3083, (2) Chemistry, Georgia State Unversity, 38 Peachtree Center AVe, Atlanta, GA 30303
To investigate nucleic acids with selenium derivatization for X-ray crystallography, we report here the first synthesis of the 2'-methylseleno-ribothymidine and 4-Se-thymidine phosphoramidite, as well as their incorporation into oligonucleotides by solid-phase synthesis with over 99% coupling yield. The crystal structure of the modified duplex, [d(GTSeGTACAC)]2, was also determined at 1.4 Å resolution using the multiwavelength anomalous dispersion (MAD) technique, revealing that this SeNAs (Selenium Nucleic Acids) strategy did not cause structure perturbation. In addition, we observed that this modification could greatly facilitate crystal growth with higher diffraction quality. This SeNAs strategy will have great potential for the structure and function investigation of nucleic acids.

 

Biologically Active Molecules
8:00 AM-12:00 PM, Tuesday, April 8, 2008 Morial Convention Center -- Rm. R05, Oral

Division of Organic Chemistry

The 235th ACS National Meeting, New Orleans, LA, April 6-10, 2008