Synthesis of p-amino-WNA derivatives to enhance the stability of the anti-parallel triplex

We have previously developed W-shaped nucleoside analogs (WNAs) having a nucleobase and an aromatic ring for the formation of the unnatural triplex DNA. Modification of an aromatic ring of WNA is highly effective regarding the stability of the triplex DNA. In this study, we designed new WNA analogs having the p-aminobenzene as an aromatic ring, which were synthesized via the Curtius–Yamada rearrangement. Based on the evaluation of the triplex formation with p-amino-WNA-TFO, it has been shown that the amino group may produce a non-selective interaction with the phosphate backbone of the target duplexes. These results indicate that the amino modification is useful to overcome the sequence-dependence of the TFO containing WNA analogs. [Display omitted]