Remarkable stabilization of antiparallel DNA triplexes by strong stacking effects of consecutively modified nucleobases containing thiocarbonyl groups

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Abstract

The consecutive arrangement of 2′-deoxy-6-thioguanosines (s6Gs) and 4-thiothymidines (s4Ts) in antiparallel triplex-forming oligonucleotides (TFOs) considerably stabilized the resulting antiparallel triplexes with high base recognition ability by the strong stacking effects of thiocarbonyl groups. This result was remarkable because chemical modifications of the sugar moieties and nucleobases of antiparallel TFOs generally destabilize triplex structures. Moreover, in comparison with unmodified TFOs, it was found that TFOs containing s6Gs and s4Ts could selectively bind to the complementary DNA duplex but not to mismatched DNA duplexes or single-stranded RNA.

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Acknowledgment

This study was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

References and notes (10)

  • V.A. Bloomfield et al.

    Nucleic Acids

    (2000)
    M.G.M. Purwanto et al.

    Curr. Org. Chem.

    (2003)
    M.D. Frank-Kamenetskii et al.

    Ann. Rev. Biochem.

    (1995)
  • V.N. Soyfer et al.

    Triple-Helical Nucleic Acids

    (1996)
  • J. Bijapur et al.

    Nucleic Acids Res.

    (1802)
    V. Roig et al.

    J. Am. Chem. Soc.

    (2003)
    D.A. Rusling et al.

    Nucleic Acids Res.

    (2009)
    S.M.A. Rahman et al.

    Angew. Chem., Int. Ed.

    (2007)
    J.S. Li et al.

    J. Org. Chem.

    (2005)
    Y. Hari et al.

    Chem. Commun.

    (2011)
    V. Malnuit et al.

    Org. Biomol. Chem.

    (2011)
    C. Lou et al.

    Med. Chem. Commun.

    (2011)
  • J.E. Gee et al.

    Biochemistry

    (1995)
    S.S. Ririe et al.

    Biochem. Biophys. Res. Commun.

    (1998)
    R.H. Durland et al.

    Bioconjugate Chem.

    (1995)
    J. Basye et al.

    Nucleic Acids Res.

    (2001)
    S.P. Parel et al.

    Nucleic Acids Res.

    (2001)
    D. Renneberg et al.

    ChemBioChem

    (2004)
  • J.F. Mouscadet et al.

    Biochemistry

    (1994)
There are more references available in the full text version of this article.

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