Targeting of Antisense: Synthesis of Steroid-Linked and Steroid-Bridged Oligodeoxynucleotides

Abstract

Steroid-linked oligonucleotides could be used as antisense drugs targeted to specific steroid receptors on selected cells. Phosphoramidites of desoxycorticosterone and 21-acetoxypregnenolone have been synthesized and characterized. They have been attached by solid-phase synthesis to the 5′-terminus of thymidine and of oligodeoxynucleotides. The 3-hydroxy group of pregnenolone has also been used to attach a second oligomer at its 3′-terminus. The steroid acts as a rigid bridge between the two noncomplementary oligomers, compared to a flexible triethylene glycol linker that was also prepared. If the two oligomers are complementary to different sites on the same mRNA, a bridged noncomplementary dimer could act as a bifunctional antisense molecule.