Synthesis of and triplex formation in oligonucleotides containing 2'-deoxy-6-thioxanthosine

Abstract

This study aimed to synthesize triplex-forming oligonucleotides (TFOs) containing 2'-deoxy-6-thioxanthosine (s⁶X) and 2'-deoxy-6-thioguanosine (s⁶Gs) residues and examined their triplex-forming ability. Consecutive arrangement of s⁶X and s⁶Gs residues increased the triplex-forming ability of the oligonucleotides more than 50 times, compared with the unmodified TFOs. Moreover, the stability of triplex containing a mismatched pair was much lower than that of the full-matched triplex, though s⁶X could form a s⁶X-GC mismatched pair via tautomerization of s⁶X. The present results reveal excellent properties of modified TFOs containing s⁶Xs and s⁶Gs residues, which may be harnessed in gene therapy and DNA nanotechnology.

Keywords: DNA nanotechnology; Gene therapy; Thioxanthosine; Triplex-forming oligonucleotide.