-Acyl-2-Thioethyl: A Convenient Base-Labile Protecting Group for the Synthesis of siRNAs Containing 5'-Vinylphosphonate.

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.