Recognition of CG interrupting site by W-shaped nucleoside analogs (WNA) having the pyrazole ring in an anti-parallel triplex DNA

Yosuke Taniguchi, Yuko Uchida, Tomoko Takaki, Eriko Aoki, Shigeki Sasaki

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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-βAP in the 3′G-WNA-G-5′ sequence formed a stable triplex with selectivity to the CG interrupting site where the previous WNA-βC did not induce the triplex formation.

Original languageEnglish
Pages (from-to)6803-6810
Number of pages8
JournalBioorganic and Medicinal Chemistry
Volume17
Issue number19
DOIs
Publication statusPublished - Oct 1 2009

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Nucleosides
Oligonucleotides
Bearings (structural)
triplex DNA
pyrazole
Stabilization

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

Cite this

Recognition of CG interrupting site by W-shaped nucleoside analogs (WNA) having the pyrazole ring in an anti-parallel triplex DNA. / Taniguchi, Yosuke; Uchida, Yuko; Takaki, Tomoko; Aoki, Eriko; Sasaki, Shigeki.

In: Bioorganic and Medicinal Chemistry, Vol. 17, No. 19, 01.10.2009, p. 6803-6810.

Research output: Contribution to journalArticle

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