Tsubaki Kouta, Hammill Matthew L, Varley Andrew J, Kitamura Mitsuru, Okauchi Tatsuo, Desaulniers Jean-Paul
Department of Applied Chemistry, Graduate School of Engineering, Kyushu Institute of Technology, 1-1 Sensui-cho, Tobata, Kitakyushu 804-8550, Japan.
Faculty of Science, University of Ontario Institute of Technology, 2000 Simcoe Street North, Oshawa, Ontario L1G 0C5, Canada.
ACS Med Chem Lett. 2020 Jun 9;11(7):1457-1462. doi: 10.1021/acsmedchemlett.0c00232. eCollection 2020 Jul 9.
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.
通过磷酸三（2,2,2 - 三氟乙基）酯的酯交换反应合成了两种不对称二核苷酸磷酸三酯。将受保护的三酯进行磷酸化以生成用于固相寡核苷酸合成的亚磷酰胺。合成了中性苯乙基磷酸修饰的小干扰RNA（siRNA），并对其基因沉默能力、siRNA链选择和核酸酶抗性进行了评估。与天然未修饰的siRNA相比，这些主链修饰的磷酸三酯siRNA有许多改进。
