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1993 Fiscal Year Final Research Report Summary

The chirality of metal complexes recognized by DNA and its significance towards biological activities

Research Project

Project/Area Number 03403009
Research Category

Grant-in-Aid for General Scientific Research (A)

Allocation TypeSingle-year Grants
Research Field 無機・錯塩・放射化学
Research InstitutionThe University of Tokyo

Principal Investigator

KURODA Reiko  Univ. of Tokyo, Chemistry, Professor, 教養学部, 教授 (90186552)

Co-Investigator(Kenkyū-buntansha) SUGIYAMA Toru  Univ. of Tokyo, Chemistry, Research Assistant, 教養学部, 助手 (40242036)
MATSUSHITA Nobuyuki  Univ. of Tokyo, Chemistry, Research Assistant, 教養学部, 助手 (80219427)
Project Period (FY) 1991 – 1993
KeywordsDNA / Metalloporphyrins / Chiral discrimanation / Induced CD / Molecular recognition
Research Abstract

The modes of DNA-porphyrin interactions are multiple and depend on the central metal ions. We have found that iron-tatrakis(4-N-methylpyridiniumyl)porphyrin possesses surprisengly high sequence preference towards the minor groove of three contiguous A.T base paris from DNase I footprinting study and affinity cleavage experiments. By analyzing CD in the porphyrins's Soret band induced by the interaction with chiral DNA, we could estimate the preferred binding modes and sequences semi-quantitatively.
A series of compounds which possess a second functional group at the end of a sidechain, as well as a compounds which possess a second functional group at the end of a sidechain, as well as a compound which substitutes a 4-N-methyl-pyridiniumyl by a tolyl group have been synthesized to study the origin of the sequence selectivity. Affinity cleavage experiments have shown that all the compounds exhibit the same high specificity and at maximum 3 positive charges are necessary for the recognition.
Molecular dynamics has shown that the most stable interaction is the side on model in the minor groove, then the major groove binding and the face on model in the minor groove. Non-bonded rather than Coulombic energy seems to contribute the stability difference.
A series of new complexes which contain a chiral ligand, [Cu(1,10-phenanthroline)(X-proline)]C1.3H_2O (X=D or L), have been synthesized and their DNA cleavage efficiency compared. The D-enantiomer cleaved DNA more efficiently than the L counterpart. The molecuar structure was determined by the single crystal X-ray diffractometry. A chiral amino acid, histidine, was introduced to the iron porphyrin. This is to study chiral recognition and the consequential difference in the DNA cleavage efficiency and base sequence specificity. The synthesis is near completion.

  • Research Products

    (26 results)

All Other

All Publications (26 results)

  • [Publications] K.Konishi: "Chiral N-substituted Porphyrins Related to Heme Inactivation Products.First Crystallographic Determination of Absolute Stereochemistry and Correlation with Circular Dichroism." Journal of the American Chemical Society. 115. 1169-1170 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] R.Kuroda: "Sequence Specific Interaction of DNA with Water-soluble Porphyrins." Nucleic Acids Symposium Series. 29. 123-124 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M.Shinomiya: "Synthesis of Novel DNA Photocleaving Agents with Potential Sequence Specificity." Tetrahedron Letters. 33. 2697-2700 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] R.Kuroda: "Chiral Discriminations and Crystal Packing.Two Diastereomeric Compounds Involving Complex Ions of D_3 Symmetry,[Tris(ethylenediamine)cobalt(III)]and[Tris(oxalato)rhodium(III)]." Inorganic Chemistry. 30. 4954-4959 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] R.Kuroda: "Analysis of DNA Binding Modes of Porphyrins as Studied by Induced Circular Dichroism Spectroscopy." Chemical Communication. (to be submitted).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] R.Kuroda: "Sequence Specific Binding Determined by Restriction Enzyme Inhibition and DNase I Footprinting Studies." Nucleic Acids Research. (to be submitted).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] R.Kuroda: "Photocleavage of DNA by the p-Nitrobenzoyl Group Covalently Linked to Proflavine." Biochem.Biophys.Res.Commun.,. 181. 1266-1270 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] R.Kuroda: "Structure of New DNA Photocleaving Agents:3,6-Diamino-10-[6-(4-nitrobenzoyloxy)hexyl]acridinium chloride and 9-[6-(4-Nitrobenzoyloxy)hexylamino]acridine Hydrochloride." Acta Cryst.,. C48. 512-515 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S.Kobayashi: "Synthesis of Thiazoe-Based DNA-Targeting Molecules Aiming at Guanine Specificity." Synlett. 59-61 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] R.Kuroda: "Origin of Sequence Specific Cleavage of DNA by Bleomycins.Sequence Specificity." Nucleic Acids Symp.Ser.,. 27. 9-10 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M.Orma: "Escherichia-coli DNA Gyrase:Genetic Analysis of gyrA and gyrB Mutations Responsible for Thermosensitive Enzyme Activity." FEBS Letters. 312. 61-65 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Kajiwara: "A Dynucleating Bis(dimethylcyclam)Ligand and Its Dinickel(II)and Zinc(II)Complexes with the Face-to-face Ring Arrangement." Inorg.Chem.,. 32. 4990-4991 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Toru Sugiyama: "Transition-metal binding site of Bleomycin.Significance of the β-Aminoalaninamide Appendage in Regulating Oxygen Activation." Heterocycles. 37. 275-282 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] R.Kuroda: "Chiral Discriminations and Crystal Packing. Two Diastereomeric Compounds Involving Complex Ions of D3 ymmetry, [Tris(ethylenediamine)cobalt(III)] and [Tris(oxalato)rhodium(III)]." Inorg. Chem.30. 4954-4959 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] R.Kuroda and M.H.Shinomiya: "Photocleavage of DNA by the p-Nitrobenzoyl Group Covalently Linked to Proflavine" Biochem. Biophys. Res. Commun. 181. 1266-1270 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] R.Kuroda and M.H.Shinomiya: "Structure of New DNA Photocleaving Agents : 3,6-Diamino-10-[6-(4-nitrobenzoyloxy)hexyl] acridinium chloride and 9-[6-(4-Nitrobenzoyloxy) hexylamino]acridine Hydrochloride" Acta Cryst. C48. 512-515 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S.Kobayashi, R.Kuroda, T.Watanabe and M.Otsuka: "Synthesis of Thiazoe-Based DNA-Targeting Molecules Aiming at Guanine Specificity" Synlett. 59-61 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M.Shinomiya and R.Kuroda: "Syuthesis of Novel DNA Photocleaving Agents with Potential Syquence Specificity" Tetrahedron Lett.33. 2697-2700 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] R.Kuroda, M.Shinomiya and M.Otsuka: "Origin of Sequence Specific Cleavage of DNA by Bleomysins" Nucleic Acids Symp. Ser.27. 9-10 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M.Orma, R.Kuroda and L.M.Fisher: "Echerichia-coli DNA Gyrase : Genetic Analysis of gyrA and gyrB Mutations Responsible for Thermosensitive Enzyme Activity." FEBS Letters. 312. 61-65 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Konichi, Y.Takahata, T.Aida, S.Inoue and R.Kuroda: "Chiral N-substituted Porphyrins Related to Home Inactivation Products. First Crystallographic Determination of Absolute Stereochemistry and Correlation with Circular Dichroism." J.Am. Chem. Soc.115. 1169-1170 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] R.Kuroda, H.Tanaka and S.Watanabe: "Sequence Specific Interaction of DNA with Water-soluble porphyrins." Nucleic Acids Symp. Ser.29. 123-124 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Kajiwara, T.Yamagishi, H.Kida, R.Kuroda and T.Ito: "A Dynucleating Bis(dimethylcyclam) Ligand and Its Dinickel (II) and Zinc (II) Complexes with the Face-to-face Ring Arrangement" Inorg. Chem.32. 4990-4991 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Toru Sugiyama, Masaji Ohno, Masakatsu Shidasaki, Masami Otsuka, Yukio Sugiura, Susumu Kobayasi, and Kenji Maeda: "Transition-metal binding site of Bleomycin. Significance of the beta-Aminoalaninamide Appendage in Regulating Oxygen Activation" Heterocycles. 37. 275-282 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] R.Kuroda, S.Watanabe and E.Takahashi: "Binding of Porphyrins and Metalloporphyrins to DNA : Sequence Binding Determined by Restriction Enzyme Inhibition and DNase I Footprinting Studies" Nucleic Acids Res.(to be submitted.).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] R.Kuroda and H.Tanaka: "Analysis of DNA Binding Modes of Porphyrins as Studied by Analysis of DNA Binding Modes of Porphyrins as Studied by Induced Circular Dichroism Spectroscopy" J.Chem. Soc. Chem. Commun.(to be submitted.).

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1995-03-27  

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