Efficient Incorporation of a Copper Hydroxypyridone Base Pair in DNA

  • Kentaro Tanaka
    Contribution from the Department of Chemistry, Graduate School of Science, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan, Institute for Molecular Science, Myodaiji, Okazaki 444-8585, Japan, and Rigaku Corporation, 3-9-12 Matsubaracho, Akishima, Tokyo 196-8666, Japan
  • Atsushi Tengeiji
    Contribution from the Department of Chemistry, Graduate School of Science, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan, Institute for Molecular Science, Myodaiji, Okazaki 444-8585, Japan, and Rigaku Corporation, 3-9-12 Matsubaracho, Akishima, Tokyo 196-8666, Japan
  • Tatsuhisa Kato
    Contribution from the Department of Chemistry, Graduate School of Science, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan, Institute for Molecular Science, Myodaiji, Okazaki 444-8585, Japan, and Rigaku Corporation, 3-9-12 Matsubaracho, Akishima, Tokyo 196-8666, Japan
  • Namiki Toyama
    Contribution from the Department of Chemistry, Graduate School of Science, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan, Institute for Molecular Science, Myodaiji, Okazaki 444-8585, Japan, and Rigaku Corporation, 3-9-12 Matsubaracho, Akishima, Tokyo 196-8666, Japan
  • Motoo Shiro
    Contribution from the Department of Chemistry, Graduate School of Science, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan, Institute for Molecular Science, Myodaiji, Okazaki 444-8585, Japan, and Rigaku Corporation, 3-9-12 Matsubaracho, Akishima, Tokyo 196-8666, Japan
  • Mitsuhiko Shionoya
    Contribution from the Department of Chemistry, Graduate School of Science, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan, Institute for Molecular Science, Myodaiji, Okazaki 444-8585, Japan, and Rigaku Corporation, 3-9-12 Matsubaracho, Akishima, Tokyo 196-8666, Japan

書誌事項

公開日
2002-09-25
DOI
  • 10.1021/ja027175o
公開者
American Chemical Society (ACS)

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説明

Recently, we reported the first artificial nucleoside for alternative DNA base pairing through metal complexation (J. Org. Chem. 1999, 64, 5002-5003). In this regard, we report here the synthesis of a hydroxypyridone-bearing nucleoside and the incorporation of a neutral Cu(2+)-mediated base pair of hydroxypyridone nucleobases (H-Cu-H) in a DNA duplex. When the hydroxypyridone bases are incorporated into the middle of a 15 nucleotide duplex, the duplex displays high thermal stabilization in the presence of equimolar Cu(2+) ions in comparison with a duplex containing an A-T pair in place of the H-H pair. Monitoring temperature dependence of UV-absorption changes verified that a Cu(2+)-mediated base pair is stoichiometrically formed inside the duplex and dissociates upon thermal denaturation at elevated temperature. In addition, EPR and CD studies suggested that the radical site of a Cu(2+) center is formed within the right-handed double-strand structure of the oligonucleotide. The present strategy could be developed for controlled and periodic spacing of neutral metallobase pairs along the helix axis of DNA.

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