We have previously developed W-shaped
nucleoside analogs (WNA) for recognition of TA and CG interrupting sites, which are the intrinsic limitation for the formation of a stable triplex
DNA by the natural triplex-forming
oligonucleotide (TFO). However, the stabilization effect of WNA is dependent on the neighboring
nucleobases at both sides of the WNA analogs within the TFO. Considering that the base is located at the
hindered site constructed of three bases of the target duplex and the TFO, it was expected that replacement of the
pyrimidine base of the WNA analog with a smaller
pyrazole ring might avoid
steric repulsion to produce a greater stability for the triplex. In this study, the new WNA analogs bearing the
pyrazole ring, 3-aminopyrazole (AP), and 4-methyl-3-pyrazole-5-on (MP) were synthesized, incorporated into the TFOs, then their stabilizing effects on the triplexes were evaluated. A remarkable success was illustrated by the fact that the TFO containing WNA-betaAP in the 3'G-WNA-G-5' sequence formed a stable triplex with selectivity to the CG interrupting site where the previous WNA-betaC did not induce the triplex formation.
