Acetal Oligonucleotide Conjugates in Antisense Strategy

Abstract

To enhance the cellular uptake for antisense oligonucleotides or analogues a lipophilic steroid moiety was linked to the 5′-O- or 2′-O-position of appropriate protected thymidine or uridine simply by acid catalysed reaction with cholesterylvinylether. The corresponding cholesteryl-acetals were derivatized to the 3′-O- or 5′-O-phosphoramidites and then introduced as 5′-end terminating agents or incorporated within the sequence of oligodeoxyribonucleotides up to a chain length of 18 bases. 3′ -end linkage was achieved by using the corresponding 2′-O-cholesteryluridine building unit, tethered via a 3′-O-/5′-O-succinate-bridge to polystyrene as solid support.