RNA interference: RISC-mediated recognition of non-canonical ribo-difluorotoluyl nucleotide: Synthesis, structure and activity

CARB 66

Kallanthottathil G. Rajeev, rajeevk@alnyalm.com1, Jie Xia1, Anne Noronha1, Ivanka Toudjarska1, Feng Li2, Akin Akinc1, Maria Frank-Kamenetsky1, Ravi Braich1, Martin Egli, martin.egli@vanderbilt.edu2, and Muthiah Manoharan, mmanoharan@alnylam.com1. (1) Drug Discovery, Alnylam Pharmaceuticals, 300 third street, Cambridge, MA 02142, (2) Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University
The 2,4-difluorotoluyl nucleoside (rF) was synthesized and incorporated into oligonucleotides to test the effect of non-canonical nucleoside mimetics on RNA interference. X-ray crystal structure of a duplex containing two rF:A pairs was resolved to study structural perturbation caused to a double stranded oligonucleotides by the modification.