A 2'-O-hexylthiotrityl adenosine phosphoramidite has been synthesized and incorporated into oligodeoxyribonucleotide (oligo) phosphodiesters and phosphorothioates. These oligos possess the lipophilic 2'-O-hexylthiotrityl group at pre-selected positions. Upon treatment with silver nitrate solution, a free thiol group was generated which was further functionalized. The new tether offers a convenient nucleophile for conjugation of various pendant moieties that would reside in the minor groove. Because of its versatility and location, the modification has a variety of potential applications, most notably as an enhancer of antisense activity.