Improved method for the solid-phase synthesis of oligoribonucleotide 5'-triphosphates.

We have developed an improved solid-phase method for the synthesis of 5'-triphosphates (5'-TPs) of oligoribonucleotides. The method is based on the use of salicyl phosphorochloridite as the phosphitylating reagent and the improvement is characterized by the use of the highly reactive pyrophosphorylating reagent tris(tetra-n-butylammonium) hydrogen pyrophosphate instead of the conventional tri-n-butylammonium salt for the nucleophilic substitution reaction to form the cyclic ester intermediate. The improved method can be used to generate oligoribonucleotide 5'-TPs efficiently and reproducibly.