Isolation of Oligodeoxynucleoside Phosphorothioate Diastereomers by the Combination of DEAE Ion-Exchange and Reversed-Phase Chromatography

Abstract

In antisense trials, oligodeoxynucleoside phosphorothioates (S-oligo) stereoisomers arise from the thiophosphate R/S configuration. We have explored effective separation of these isomers by the combination of DEAE ion-exchange (IELC) and reversed-phase (RPLC) liquid chromatography. Twenty-six S-oligos and some of the natural counterparts were examined. In the presence of DMTr at the 5′-end, isomers could be separated well by ELC, while RPLC gave good resolution in the absence of this protecting group. Combination of these two different modes leads to more effective isolation.

^aDedicated to Dr. Yoshihisa Mizuno on the occasion of his 75th birthday.

Notes

^aDedicated to Dr. Yoshihisa Mizuno on the occasion of his 75th birthday.