Synthesis and Properties of RNA Modified with Cationic Amine Internucleoside Linkage
Chandan Pal1, Michael Richter1, Eriks Rozners1
1Department of Chemistry, Binghamton University, The State University of New York, Binghamton, New York 13902, United States.
Abstract:
Chemical modifications of RNA are important tools for the development of RNA therapeutics. The present study reports a novel RNA backbone modification that replaces the negatively charged phosphate with a positively charged amine linkage. Despite being thermally destabilizing in RNA duplexes, the amine linkage caused a relatively modest decrease of activity of a modified short interfering RNA (siRNA). At position 2 of the guide strand, the amine modification strongly enhanced the specificity of siRNA while causing an ∼5-fold drop of on-target activity. These results support the future development of amines as cationic RNA modifications and novel tools to modulate protein-RNA interactions.
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