Bridged nucleic acid conjugates at 6′-thiol: synthesis, hybridization properties and nuclease resistances

The bridged nucleic acid (BNA) containing a thiol at the 6′-position in the bridged structure was synthesized from the disulfide-type BNA and conjugated with various functional molecules via the thioether or the disulfide linkage post-synthetically and efficiently in solution phase. The disulfide-linked conjugate was cleaved under reductive conditions derived from glutathione and an oligonucleotide bearing a free thiol was released smoothly. Conjugated functional molecules had great effects on duplex stability with the DNA complement. In contrast, the molecules little influenced the stability with the RNA complement. Moreover, the oligonucleotides with functional groups at the 6′-position had as high or higher resistances against 3′-exonuclease than phosphorothioate oligonucleotide (S-oligo).