2'-O-ALE (acetal levulinylester) and 2'-O-ester groups for 2'-hydroxyl protection in the solid-phase synthesis and delivery of siRNA

CARB 50

Jeremy G. Lackey, jeremy.lackey@mail.mcgill.ca, Gallant Pascal, Mathew Hassler, and Masad J. Damha, masad.damha@mcgill.ca. Chemistry, McGill University, 3420 University Street, Montreal, QC H3A 2A7, Canada
Short interfering oligoribonucleotides (siRNA) have been synthesized by solid-phase starting from monomeric 2'-O-acetal levulinylester (ALE; 2'-O-CH2-O-Lv) ribonucleoside phosphoramidite derivatives. This strategy improves upon our initial work utilizing 2'-O-levulinyl (Lv) esters as a protecting group. In addition, we have examined the use of lipases and hydrolases as ‘biocatalysts' for the large scale chemo-enzymatic synthesis of ribonucleoside synthons. Finally, we have evaluated the use of 2'-O-ester RNA conjugates to aid in cellular uptake of siRNA.
 

RNA Interference Based Therapeutics
1:25 PM-4:45 PM, Tuesday, August 21, 2007 BCEC -- 208, Oral

Division of Carbohydrate Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007