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Bioorg Med Chem Lett. 2012 Nov 15;22(22):6934-7. doi: 10.1016/j.bmcl.2012.09.009. Epub 2012 Sep 20.

Gene-silencing properties of siRNAs that contain internal amide-bond linkages.

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  • 1Faculty of Science, University of Ontario Institute of Technology, 2000 Simcoe Street North, Oshawa, Ontario, Canada L1H 7K4.


Chemically modified short interfering RNAs (siRNAs) that contain backbone amide-bonds at both 3'-overhangs and internal positions were synthesized. These siRNAs contain the modifications within both the sense and antisense strands that target the transcripts from pGL2 and pGL3. The siRNAs were synthesized via site-specific incorporation of a PNA-RNA dimer by solid-phase phosphoramidite techniques. The silencing data suggest a high degree of compatibility of amide-modified siRNAs within the RNAi pathway when located internally within the sense strand and at 3'-overhangs. Biophysical data indicates that melting temperatures of the siRNAs decrease when the modification is located internally.

Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

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