Synthesis of 5’-fluorophosphate-modified short-interfering RNAs

Abstract

We have developed an improved scheme for the synthesis of a mono-fluorinated phosphoramidite for the 5’-modification of nucleic acids using standard phosphoramidite chemistry. We describe the first report of a phosphofluoridate modified siRNA strand and have evaluated C18 HPLC for purification of modified strands from unreacted siRNA strands. Lastly, the biological activity of the high purity siRNA strands, when placed on the sense and/or antisense strand, was evaluated to assess the impact of 5’ phosphofluoridate modifications on siRNA activity.

Keywords:

• Phosphofluoridate
• RNA
• solid phase synthesis
• nucleic acid chemistry

Acknowledgements

We acknowledge the Natural Sciences and Engineering Research Council of Canada (NSERC) for funding and Ifrodet Giorgees for performing mass spec samples.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

We acknowledge the Natural Sciences and Engineering Research Council of Canada (NSERC) for funding and Ifrodet Giorgees for performing mass spec samples.