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Synthesis and Evaluation of Neutral Phosphate Triester Backbone-Modified siRNAs.

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.

SUBMITTER: Tsubaki K

PROVIDER: S-EPMC7357222 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Synthesis and Evaluation of Neutral Phosphate Triester Backbone-Modified siRNAs.

Tsubaki Kouta K Hammill Matthew L ML Varley Andrew J AJ Kitamura Mitsuru M Okauchi Tatsuo T Desaulniers Jean-Paul JP

ACS medicinal chemistry letters 20200609 7

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 ...[more]

PMID: 32676154

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