Synthesis of thiolated oligonucleotides without capping and without recirculation of the thiolating agent

Abstract

The invention relates to a novel process for the production of a linear P-linked oligonucleotide which is characterized by a sulfurization step which requires no recirculation of the sulfurizing agent and which does not involve a separate capping step in the stepwise addition of nucleoside residues to the 5'-terminus of the growing chain. The novel process allows for shorter times for each reaction cycle in the oligonucleotide assembly which amounts in a substantial time saving for the manufacture of longer oligonucleotides.