Minor-groove-modulating adenosine replacements control protein binding and RNAi activity in siRNAs.

ABSTRACT: Short-interfering RNAs (siRNAs) are common tools in molecular biology; however, the development of RNAi-based therapeutics is limited by immunostimulatory and nonspecific effects mediated by off-target RNA-binding proteins. The RNA-dependent protein kinase (PKR) and adenosine deaminase that acts on RNA 1 (ADAR1) are two proteins implicated in RNAi off-target effects and share a common means of interaction with siRNAs through double-stranded RNA binding motifs (dsRBMs). Here we report the site-specific introduction of N²-propargyl 2-aminopurine into siRNAs and subsequent conversion to two bulky products via copper-catalyzed azide alkyne cycloaddition (CuAAC) with either N-azidoacetyl-mannosamine azide or N-ethylpiperidine azide. We observed position-specific effects on RNAi activity for mod

SUBMITTER: Peacock H 

PROVIDER: S-EPMC3003776 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature