In 2018 a novel platform for the synthesis of stereodefined phosphorothioate oligonucleotides was reported. This platform uses PSI (phosphorous-sulfur incorporation) reagents which are designed to keep phosphorus in the final P(V) oxidation state throughout the synthetic cycle. In our expansion of the P(V) work to synthesize therapeutically useful antisense oligonucleotides (i.e., LNA gapmers), an unexpected 3’-&gt;5’ acyl migration from preloaded LNA Q-linker support was encountered. A novel PEG-tethered unylinker was designed to avoid this rearrangement while withstanding the strongly basic coupling environment. A general automation cycle was established on a Mermade oligonucleotide synthesizer to incorporate stereodefined phosphorothioate, phosphodiester and phosphorodithioate linkages within the target oligonucleotides.

Development of a novel linker for automated oligonucleotide synthesis using a P(V) platform

Fall 2022 abstracts, posters, and presentations will launch in mid-September.

ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.