Efficient Solid-Phase Chemical Synthesis of 5′-Triphosphates of DNA, RNA, and their Analogues

A robust, reproducible, and scalable method for the solid-phase synthesis of 5′-triphosphates of DNA, RNA, and their chemically modified analogues using 5′-<i>H</i>-phosphonate intermediates is described. 5′-Triphosphates of oligonucleotides with varying lengths and sequences containing different 5′-terminal nucleotides, with and without internal sugar-backbone modifications, were efficiently prepared as crude products or further purified by HPLC.