An Improved P(V) Thio-Oligonucleotide Synthesis Platform

Three critical advances in simplifying the adoption of P(V)-based stereopure, phosphorothioate-containing oligonucleotide synthesis are reported. A more inexpensive phosphorus–sulfur incorporation reagent (ΨBr) is introduced, a robust linker system was developed, and a systematic study of common nucleobase protecting groups was performed to significantly reduce the barrier to adoption of this technology.