Synthesis and Evaluation of Neutral Phosphate Triester Backbone-Modified siRNAs
journal contributionposted on 2020-06-15, 04:46 authored by Kouta Tsubaki, Matthew L. Hammill, Andrew J. Varley, Mitsuru Kitamura, Tatsuo Okauchi, Jean-Paul Desaulniers
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.