Effects of 5-substituted pyrimidine nucleoside bases of WNA on stability of triplex DNA.

Abstract

Triplex-forming oligonucleotides (TFOs) are potential DNA-targeting molecules, but their recognizable duplexes are limited to homopurine:homopyrimidine sequences by interruption of pyrimidine bases in the purine strand. Despite numerous studies, this problem has not been generally solved. We have recently demonstrated that the new nucleoside analogues, WNA-betaT and WNA-betaC exhibit selective stabilization of the triplexes at a TA and a CG interrupting site, respectively. However, subsequent investigations have shown that there are limitations in recognizable sequences by these analogs. In this study, we performed further systematic investigation on WNA analogs by synthesizing a variety of WNA analogs having 5-substituted cytosine and uracil, and found that WNA-betaFU exhibit high CG-selectivity.