4.5 Article

Synthesis and Evaluation of Neutral Phosphate Triester Backbone-Modified siRNAs

期刊

ACS MEDICINAL CHEMISTRY LETTERS
卷 11, 期 7, 页码 1457-1462

出版社

AMER CHEMICAL SOC
DOI: 10.1021/acsmedchemlett.0c00232

关键词

Short interfering RNA; backbone modification; phosphate triester; off-target effect

资金

  1. Natural Sciences and Engineering Research Council (NSERC)
  2. Institute of Rheological Functions of Food in Japan

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Two unsymmetrical dinucleotide phosphate triesters were synthesized via transesterification from tris(2,2,2trifluoroethyl) 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 genesilencing 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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