Recognition of CG interrupting site by W-shaped nucleoside analogs (WNA) having the pyrazole ring in an anti-parallel triplex DNA.
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.
Taniguchi
Yosuke
Y
Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Uchida
Yuko
Y
Takaki
Tomoko
T
Aoki
Eriko
E
Sasaki
Shigeki
S
D003596:Cytosine; D004247:DNA / Q000138:chemical synthesis* / Q000737:chemistry; D006147:Guanine; D009690:Nucleic Acid Conformation; D009705:Nucleosides / Q000138:chemical synthesis / Q000737:chemistry*; D011720:Pyrazoles / Q000737:chemistry
C436945:3-aminopyrazole; D009705:Nucleosides; D011720:Pyrazoles; C051802:triplex DNA; C031280:pyrazole; D006147:Guanine; D003596:Cytosine; D004247:DNA