Promiscuous 8-alkoxyadenosines in the guide strand of an siRNA: modulation of silencing efficacy and off-pathway protein binding.

ABSTRACT: 8-Alkoxyadenosines have the potential to exist in anti or syn conformations around the glycosidic bond when paired opposite to U or G in the complementary strands, thereby placing the sterically demanding 8-alkoxy groups in the major or minor groove, respectively, of duplex RNA. These modified bases were used as "base switches" in the guide strands of an siRNA to prevent off-pathway protein binding during delivery via placement of the alkoxy group in the minor groove, while maintaining significant RNAi efficacy by orienting the alkoxy group in the major groove. 8-Alkoxyadenosine phosphoramidites were synthesized and incorporated into the guide strand of caspase 2 siRNA at four different positions: two in the seed region, one at the cleavage junction, and another nearer to the 3'-end of the

SUBMITTER: Ghanty U 

PROVIDER: S-EPMC3491887 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature