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Synthesis of artificial phosphatases for the purpose of controling protein function

Research Project

Project/Area Number 08672558
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 医薬分子機能学
Research InstitutionHIROSHIMA UNIVERSITY

Principal Investigator

KOIKE Tohru  Hiroshima University School of Medicine, Associate Professor, 医学部, 助教授 (90186586)

Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1997: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1996: ¥1,300,000 (Direct Cost: ¥1,300,000)
KeywordsPhosphoryl Protein / Intelligent Molecule / Artificila Phosphatase / 亜鉛酵素
Research Abstract

We have synthesized dinuclear zinc (II) crypate having novel functions that may be relevant to the properties of dinuclear metal-containing phosphatases. In aqueous solution, as a substrate phosphomonoester dianion approaches to bridge both zinc (II) ions, the apical NH's dissociate and one of them attacks the phosphate to perform a phosphoryl-transfer reaction, yielding a new phosphoramide-containing cryptate. The present new findings may serve to rationalize the essence of dinuclear metallophosphatases, inhibition by inorgganic phosphate, or stabilization of the phosphoryl-transfered intermediates.
A lipophilic zinc (II) complex has been synthesized and fully characterized. It was demonstrated that in co-micellar solution with a neutral surfactant Triton X-100, the zinc complex forms Zn-hydroxideat alkaline pH.The Zn-hydroxide is the nucleophilic catalyst in the co-micelle for hydrolysis of 4-nitrophenyl acetate, phosphotriester and phosphodiester monoanion. This study suggests that the lipophilic zinc complex in the presence of the surfactant may be an extremely promosing candidate for disposal of nerve gases.
We have syntehsized novel di- and tri-nuclear macrocyclic polyamine zinc (II) complexes as active center models for zinc (II) -containing phosphatase. Those complexes have strong binding affinity to phosphomonoester dianions.

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Tohru Koike: "Novel Properties of Cooperative Dinuclear Zinc (II) Ions : The Selective Recognition of Phosphomonoesters and Their P-O Bond Cleavage by a New Dinuclear Zinc (II) Cryptate" Journal of American Chemical SOciety. 118. 3091-3099 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Eiichi Kimura: "Hydrolysis of Lipophilic Esters Catalyzed by a Zinc (II) Complex of a Long Alkyl-Pendet Macrocyclic Tetraamine in Micellar Solution" Journal of American Chemical SOciety. 118. 10963-10970 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Eiichi Kimura: "A Tris (Zinc (II)-cyclen) Complex as a New Receptor for Phosphate Dianions in Aqueous Solution" Journal of American Chemical SOciety. 119. 3068-3076 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Eiichi Kimura: "Why are Zinc Phosphatases Multinuclear?" J. Synth. Org. Chem., Jpn.55. 1052-1061 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Eiichi Kimura: "Advances in Zinc Enzyme Models by Small, Mononuclear Zinc (II) Complexes" Structure and Bonding. 89. 1-28 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tohru Koike: "Novel Properties of Cooperative Dinuclear Zinc (II) Ions : The Selective Recognition of Phosphomonoesters and Their P-O Bond Cleavage by a New Dinuclear Zinc (II) Cryptate" Journal of American Chemical Society. 118. 3091-3099 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Eiichi Kimura: "Hydrolysis of Lipophilic Esters Catalyzed by a Zinc (II) Complex of a Long Alkyl-Pendant Macrocyclic Tetraamine in Micellar Solution" Journal of American Chemical Society. 118. 10963-10970 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Eiichi Kimura: "A Tris (Zinc (II) -cyclen) Complex as a New Rceptor for Phosphate Dianions in Aqueous Solution" Journal of American Chemical Society. 119. 3068-3076 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Eiichi Kimura: "Why are Zinc Phosphatases Multinuclear?" J.Synth.Org.Chem.Jpn. 55. 1052-1061 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Eiichi Kimura: "Advances in Zinc Enzyme Models by Small, Mononuclear Zinc (II) Complexes" Structure and Bonding. 89. 1-28 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Eiichi Kimura: "A Tris (Zinc (II)-cyclen) Complex as a New Receptor for Phosphate Dianions in Aqueous Solution" Journal of American Chemical Society. 119・14. 3068-3076 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Eiichi Kimura: "Why are Zinc Phosphatases Multinuclear?" J.Synth.Org.Chem., Jpn. 55・11. 1052-1061 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Eiichi Kimura: "Advances in Zinc Enzyme Models by Small, Mononuclear Zinc (II) Complexes" Structure and Bonding. 89. 1-28 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tohru Koike: "Novel Properties of Cooperative Dinuclear Zinc(II)Ions : The Selective Recognition of Phosphomonoesters and Their P-O Bond Cleavage by a New Dinuclear Zinc(II)Cryptate" Journal of American Chemical Society. 118・13. 3091-3099 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Eiichi Kimura: "Hydrolysis of Lipophilic Esters Catalyzed by a Zinc (II) Complex of a Long Alkyl-Pendant Macrocyclic Tetraamine in Micellar Solution" Journal of American Chemical Society. 118・45. 10963-10970 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Eiichi Kimura: "A Tris(Zinc(II)-cyclen) Complex as a New Receptor for Phosphate Dianions in Aqueous Solution" Journal of American Chemical Society. 119(in press). (1997)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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