Ionis Pharmaceuticals Inc., 2855 Gazelle Ct, Carlsbad, CA 92008, USA.
Molecules. 2019 Jan 9;24(2):225. doi: 10.3390/molecules24020225.
We recently reported that ()-5'-vinylphosphonate (5'-VP) is a metabolically-stable phosphate mimic for siRNA and demonstrated that 5'-VP improves the potency of the fully modified siRNAs in vivo. Here, we report an alternative synthesis of 5'-VP modified guide strand using -pivaloyl-2-thioethyl (Bu-SATE) protecting group. The Bu-SATE group is readily removed during the final cleavage of the oligonucleotide from the solid support and providing a more convenient route for the synthesis of siRNA guide strand carrying a 5'-vinylphosphonate.
我们最近报道称，5'-乙烯基磷酸酯（5'-VP）是一种代谢稳定的 siRNA 磷酸类似物，并证明 5'-VP 提高了完全修饰的 siRNA 在体内的效力。在这里，我们报告了一种使用-pivaloyl-2-thioethyl（Bu-SATE）保护基替代合成 5'-VP 修饰的引导链的方法。Bu-SATE 基团在寡核苷酸从固体载体上的最后切割过程中很容易被去除，并为合成携带 5'-乙烯基磷酸酯的 siRNA 引导链提供了更方便的途径。
