A 2'-O-thiol tether in the ribose moiety of nucleic acids for conjugation chemistry.
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.
Manoharan
M
M
Department of Medicinal Chemistry, Isis Pharmaceuticals, Carlsbad CA 92008.
Tivel
K L
KL
Ross
B
B
Cook
P D
PD
D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D009943:Organophosphorus Compounds / Q000737:chemistry; D012266:Ribose / Q000737:chemistry; D013438:Sulfhydryl Compounds / Q000737:chemistry*
D008024:Ligands; D009838:Oligodeoxyribonucleotides; D009943:Organophosphorus Compounds; D013438:Sulfhydryl Compounds; D012266:Ribose