Nucleic acids are important biomacromolecules in living system. Structure determination of RNAs, DNAs, and their protein complexes can provide insights into their structures and functions. X-ray crystallography is a powerful tool for the 3-D structure determination of these biomacromolecules although heavy atom derivatization for phase determination, a long-standing major problem in X-ray crystallography, has largely slowed down structural determination of nucleic acids with novel folds. Selenium has proven to be a very effective anomalous scattering center in X-ray crystallography via the Multiwavelength Anomalous Dispersion (MAD) technique. More excitingly, the introduction of the selenium functionality into nucleic acids significantly facilitates the growth of nucleic acid crystals for crystallography. In our quest to better understand nucleic acid structure and function, we continue to explore the possible benefits of selenium by focusing on the enzymatic synthesis of Se-DNAs and Se-RNAs. We will report here the chemical synthesis of the Se-nucleobase-derivatized triphosphates and the enzymatic synthesis of selenium-derivatized nucleic acids (SeNA) by the polymerases, which also provides new insights into the macromolecular structures and interactions.

Acknowledgement: This work has been supported by NIH (GM069703) and NSF (MCB-0517092).

Selected publications:

1. Jozef Salon, Jia Sheng, Jiansheng Jiang, Guexiong Chen, Julianne Caton-Williams, Zhen Huang, Journal of American Chemical Society, 2007, 129, 4862-4863.

2. Jiansheng Jiang, Jia Sheng, Nicolas Carrasco, and Zhen Huang, Nucleic Acids Research, 2007, 35, 477-485.

3. Jia Sheng, Jiansheng Jiang, Jozef Salon, and Zhen Huang, Organic Letters, 2007, 9, 749-752.