Efficient substrate cleavage catalyzed by Hammerhead ribozymes derivatized with selenium

BIOL 113

Zhen Huang, Huang@gsu.edu1, Gary E. Brandt, gbrandt1@student.gsu.edu1, and Nicolas N. Carrasco, Carrasco@brooklyn.cuny.edu2. (1) Department of Chemistry, Georgia State University, 38 Peachtree Center Avenue, Atlanta, GA 30303-3083, (2) Department of Biochemistry and Chemistry, Brooklyn College, 2900 Bedford Ave., Brooklyn, NY 11210
As oxygen and selenium are in the same group (Family VI) in the Periodic Table, the atom-specific mutagenesis by replacing nucleotide oxygen with selenium can provide insights on structure and function of nucleic acids. We will present transcription of the Se-derivatized hammerhead ribozymes with all nucleoside 5'-(á-P-seleno)triphosphates (NTPáSe, including A, C, G, and U) and their activity studies. We have demonstrated the catalytic activities of these Se-derivatized hammerhead ribozymes by cleaving the RNA substrate, and we found that these phosphoroselenoate ribozymes can be as active as the native. These hammerhead ribozymes mutagenized atom-specifically by selenium reveal the close relationship between the catalytic activities and the replaced oxygen atoms, which provides the insights of the oxygen participation in catalysis and intramolecular interaction.

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