Synthesis and Evaluation of Neutral Phosphate Triester Backbone-Modified siRNAs
Kouta Tsubaki1,2, Matthew L Hammill2, Andrew J Varley2
1Department of Applied Chemistry, Graduate School of Engineering, Kyushu Institute of Technology, 1-1 Sensui-cho, Tobata, Kitakyushu 804-8550, Japan.
Abstract:
Two unsymmetrical dinucleotide phosphate triesters were synthesized via transesterification from tris(2,2,2-trifluoroethyl) phosphate. The protected triesters were phosphytilated to generate phosphoramidites for solid-phase oligonucleotide synthesis. Neutral phenylethyl phosphate-modified short-interfering RNAs (siRNAs) were synthesized and evaluated for their gene-silencing ability, siRNA strand selection, and resistance to nucleases. These backbone-modified phosphate triester siRNAs offer many improvements compared to natural unmodified siRNAs.
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