Datta Dhrubajyoti, Kundu Jayanta, Miller Patrick, Khan Mehreen S, Salinas Juan, Qin June, LeBlanc Sarah, Nguyen Tuyen, Peng Haiyan, Theile Christopher S, Egli Martin, Manoharan Muthiah
Alnylam Pharmaceuticals, 675 West Kendall Street, Cambridge, MA 02142, USA.
Department of Biochemistry, Vanderbilt University, School of Medicine Nashville, TN 37232, USA.
Chem Commun (Camb). 2025 Apr 29;61(36):6659-6662. doi: 10.1039/d5cc00348b.
A phosphate or a phosphate mimic at the 5' terminus of the antisense strand of a small interfering RNA (siRNA) is required for efficient loading into the RISC complex through the MID domain binding pocket of Ago2. Introduction of 5'--vinylphosphonate improves this binding and siRNA potency, but the isomer does not. Here, we demonstrate that both the and isomers of 6'-vinylphosphonate at the 5' ends of antisense strands of siRNAs have equivalent potencies.
小干扰RNA（siRNA）反义链5'末端的磷酸酯或磷酸酯类似物是通过Ago2的MID结构域结合口袋有效加载到RISC复合物中所必需的。引入5'-乙烯基膦酸酯可改善这种结合和siRNA的效力，但该异构体则不然。在这里，我们证明了siRNAs反义链5'端6'-乙烯基膦酸酯的和异构体具有同等效力。
