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Creation of Novel Macrocyclic Compounds that Selectively Recognize Nucleobases to Control Gene Expression

Research Project

Project/Area Number 07458144
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Bioorganic chemistry
Research InstitutionHIROSHIMA UNIVERSITY

Principal Investigator

KIMURA Eiichi  HIROSHIMA UNIVERSITY,SCHOOL OF MEDICINE,PROF., 医学部, 教授 (30034010)

Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥7,800,000 (Direct Cost: ¥7,800,000)
Fiscal Year 1996: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1995: ¥5,600,000 (Direct Cost: ¥5,600,000)
KeywordsMacrocyclic polyamines / Dinuclear zinc complex / Nucleotide recognition / Terbium complex / Anti-HIV activity / Nerve gas / Detoxification / Zinc fluorophore / ダンシルペンダント / 大環状テトラアミン / 二核錯体 / ヌクレオシド / 核酸認識 / 亜鉛錯体 / X線結晶構造 / 蛍光
Research Abstract

1995
1)Several di- and trinuclear macrocyclic polyamine complexes have been synthesized, which recognize specific nucleotides (uridien, Thymidine) in oligomers, and barbital. The jstrong interactions were studied by pH-metric titrations and NMR and UV spectroscopic methods.
2)A novel polyamine cryptate was synthesized, whose dizinc complex selectively cleaves phosphomonoesters. Intrinsic zinc prooperties in alkaline phosphatase are disclosed.
3)A new macrocyclic polyamine-terbium complex waas synthesized and its crystal structure was determined by X-ray study. This complex selectively recognizes guamine among nucleobases by emitting fluorescence.
1996
1)The newly synthesized bis (Zn^<II>-cyclen) complexes were shown to possess very strong anti-HIV activity in vitro.
2)The newly synthesized Zn^<II>-cyclen complexes denature poly A-poly U and poly dA-poly dT at rom temperature. These are the first examples of small molecules that effectively modify DNA double strands.
3)A New biomimetic zinc fluorophore, dansyl-pendant cyclen, was synthesized, which has a great potential for analysis of trace zinc in cells.
4)A new cyclen attached with a long alkyl chain was synthesized. Its zinc complex is one of the best catalysis to detoxify nerve gases like salin.

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • Research Products

    (55 results)

All Other

All Publications (55 results)

  • [Publications] T.Koike et.al.: "The Catalytic Carboxyester Hydrolysis by a New Zinc (II) Complex with an Alcohol-Pendant" J.Am.Chem.Soc.117(4). 1210-1219 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Y.Kobayashi et al.: "Molecular Structure of Chloro [2S,5S,8S,11S) -2,5,8,10-tetraethyl-1,4,7,10-tetraazacyclo dodecanelzine (II) Perchlorate" Anal.Sci.11(23). 1029-1030 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Ikeda et.al: "Molecular Recognition of Terephthalic Acid by Supramolecular Self-Assembly of an Acridine-Pendant Cyclen-ZnII-Complex" Angew.Chem.,Int.Ed.Engl.34(6). 663-664 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Y.Kodama et.al: "Phosphodieter Hydrolysis by a New Zinc (II) Macrocyclic Tetraamine Complex with an Alcohol Pendant : Elucidation of the Roles of Ser-102 and ZInc (II) in Alkaline Phosphatase" J.Am.Chem.Soc. 117(32). 8304-8311 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Fujioka et.al: "A new Bis (Zinc (II) -Cyclen) Complex as a Novel Chelator for Barbiturates and Phosphates" Heterocyles. 42(2). 775-787 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] E.Kimura et al.: "Zinc Complexes as Targeting Agents for Nucleic Acids" "Metal Ions in Biological Systems" ed.by A.Sigel and H.Sigel,Marcel Dekker,Inc,. 33. 29-52 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Y.Inouye et.al: "Differntial Contribution of Metal Complexation and Dimerization to the Chemotherapeutic Potential of Bicyclen-Zn2^<II> Complex against Human Immunodeficiency Virus" Biol.Pharm.Bull.19(3). 456-458 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Koike et.al: "Novel Properties of Cooperative Dinuclear Zinc (II) Ions : The Selective Recognition of phosphomonoesters and Their P-O Ester Bond Cleavage by a New Dinuclear Zinc (II)" J.Am.Chem.Soc. 118(13). 3091-3099 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Koike et.al: "Bis (Zn^<II>-Cyclen) Complex as a Novel Receptor of Barbiturates in Aqueous Solution." Chem.Europ.J.2(6). 617-623 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] X.H.Bu et.al: "Stabilization of Nickel (III) ion by New Macrocyclic Dioxotetraamines Bearing Functional Pendant Donors" Polyhedron. 15. 161-163 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Y.Kodama et.al: "A New Cyclam with a Triphenylphosphine-pendant and its Metal Complexes" Inorg.Chim.Acta. 246. 151-158 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Koike et.al: "Metalloenzyme Models that Answer Mysteries Surrounding the Intrinsic Properties of Zn^<II>" Comprehensive Supramoleculaar Chemistry' 10,Pergamon. 429-444 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] E.Kimura: "Creation of new Supramoleculaar Science with Macrocyclic Polyamines" (1996 Pharmaceutical Society of Japan Award Review) Yakugaku Zasshi,. 116(8). 587-605 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Hashimoto et.al: "Hydrolysis of Lipophilic Esters Catalyzed by a Zinc (II) Complex of a Long Alkyl-Pendant Macrocyclic Tetraamine in Micellar Solution" J.Am.Chem.Soc.118(45). 10963-10970 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] X.H.Bu et.al: "Synthesis,Crystal Structure and Properties of the Copper (II) Complex of a New Dioxocyclam Appended wite Two 8-Methylguinolines as Additional Donor Pendants" Inorg.Chim.Acta.249. 125-130 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Koike et.al: "Intrinsic Properties of Zinc (II) Ion Pertinent to Zinc Enzymes" Advance in Inorganic Chemistry',Ed.by A.G.Sykes,Academic Press,. 44. 229-261 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Watanabe et al.: "A Novel Biomimetic Zinc (II) -Fluorophore,Dansylamin oethyl-Pendant Macrocyclic Tetraamine 1,4,7,10-Tetraazacyclododecane (Cyclen)" J.Am.Chem.Soc.118(50). 12696-12703 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tohru Koike, Satoko Kajitani, Ikushi Nakamura, Eiichi Kimura, and Motoo Shir: ""The Catalytic Carboxyester Hydrolysis by a New Zinc (II) Complex weith an Alcohol-Pendant Cyelen (1-(2-Hydroxyethyl)-1,4,7,10-tetraazacyclododecane) : A Novel Model for Indirect Activation of the Serine Nucleophile by Zinc (II) in Zinc Enzymes"" J.Am.Chem.Soc.117. 1210-1219 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kimiko Kobayashi, Mitsuhiko Shionoya, Eiichi Kimura, Kaoru Tsuboyama, and Sei Tsuboyama: ""Molecular Structure of Chloro [(2S,5SS,8S,11S)-2,5,8,11-tetraethyl-1,4,7,10-tetraazacyclo-dodecane] zinc (II) Perchlorate"" Anal.Sci.11. 1029-1030 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Eiichi Kimura, Takuaya Ikeda, Mitsuhiko Shionoya, and Motoo Shiro: ""Molecular Recognition of Terephthalic Acid by Supramolecular Self-Assembly of an Acridine-Pendant Cyclen-Zn^<II>-Complex"" Angew.Chem., Int.Ed.Engl.34(6). 663-664 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Eiichi Kimura, Yorimitsu Kodama, Tohru Koike, and Motoo Shiro: ""Phosphodiester Hydrolysis by a New Zinc (II) Macrocycli Tetraamine Complex with an Alcohol Pendant : Elucidation of the Roles of Se-102 and Zinc (II) in Alkaline Phosphatase"" J.Am.Chem.Soc.117. 8304-8311 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Haruto Fujioka, Tohru Koike, Naoka Yamada, and Eiichi Kimura: ""A New Bis (Zinc (II) -Cyclen) Complex as a Novel Chelator for Barbiturates and Phosphates"" Heterocycles. 42,2. 775-787 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] E.Kimura and M Shionoya: ""Zinc Complexes as Targeting Agents for Nucleic Acids"" in "Metal Ions in Biological Systems" ed.by A.Sigel and H.Sigel, Marcel Dekker, Inc. 33. 29-52 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Y.Inouye, T.Kanamori, T.Yoshida, T.Koike, M.Shionoya, H.Fujioka, and E.Kimura: ""Differential Contribution of Metal Complexation and Dimerization to the Chemotherapeutic Potential of Bicyclen-Zn2^<II> Complex against Human Immunodeficiency Virus"" Biol Pharm.Bull.19(3). 456-458 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Koike, M.Inoue, E.Kimura, and M.Shiro: ""Novel Properties of Cooperative Dinuclear Zinc (II) Ions : The Selective Recognition of Phosphomonoesters and Their P-O Ester Bond Cleavage by a New Dinuclear Zinc (II) Cryptate"" J.Am.Chem.Soc.118. 3091-3099 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Koike, M.Takashige, E.Kimura, H.Fujioka, and M.Shiro: ""Bis (Zn^<II>-Cyclen) Complex as a Novel Receptor of Barbiturates in Aqueous Solution."" Chem.Europ.J.2. 617-623 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] X.H.Bu, D.L.An, X.C.Cao, Y.T.Chen, M.Shionoya, E.Kimura: ""Stabilization of Nickel (III) ion by New Macrocyclic Dioxotetraamines Bearing Functional Pendant Donors"" Polyhedron. 15. 161-163 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] E.Kimura, Y.Kodama, M.Shionoya, and T.Koike: ""A New Cyclam with a Triphenylphosphine-pendant and its Metal Complexes."" Inorg.Chim.Acta. 246. 151-158 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] E.Kimura and T.Koike: ""Metalloenzyme Models that Answer Mysteries Surrounding the Intrinsic Properties of Zn^<II>"" in 'Comprehensive Supramoleculaar Chemistry' 10, Pergamon. 429-444 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] E.Kimura: ""Creation of new Supramoleculaar Science with Macrocyclic Polyamines" (in Japanese)" (1996 Pharmaceutical Society of Japan Award Review) Yakugaku Zasshi. 116. 587-605 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] E.Kimura, H.Hashimoto, and T.Koike: ""Hydrolysis of Lipophilic Esters Catalyzed by a Zinc (II) Complex of a Long Alkyl-Pendant Macrocyclic Tetraamine in Micellar Solution"" J.Am.Chem.Soc.118. 10963-10970 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] X.H.Bu, Z.H.Zhang, D.L.An, Y.T.Chen, M.Shionoya, and E.Kimura: ""Synthesis, Crystal Structure and Properties of the Copper (II) Complex of a New Dioxocyclam Appeded with Two 8-Methylquinolines as Additional Donor Pendants"" Inorg.Chim.Acta.249. 125-130 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] E.Kimura and T.Koike: ""Intrinsic Properties of Zinc (II) Ion Pertinent to Zinc Enzymes"" in 'Advance in Inorganic Chemistry', Ed.by A.G.Sykes, Academic Press. 44. 229-261 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Koike, T.Watanabe, S.Aoki, E.Kimura, and M.Shiro: ""A Novel Biomimetic Zinc (II)-Fluorophore, Dansylamisoethyl-Pendant Macrocyclic Tetraamine 1,4,7,10-Tetraazacyclododecane (Cyclen)"" J.Am.Chem.Soc.118. 12696-12703 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Y. Kodama et. al: "Phosphodiester Hydrolysis by a New Zinc (II) Macrocyclic Tetraamine Complex with an Alcohol Pendant : Elucidation of the Roles of Ser-102 and ZInc (II) in Alkaline Phosphatase" J. Am. Chem. Soc. 117 (32). 8304-6311 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] H. Fujioka et. al.: "A new Bis (Zine (II) -Cyclen) Complex as a Novel Chelator for Barbiturates and Phosphates" Heterocycles. 42 (2). 775-787 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] E. Kimura et. al: "Zinc Complexes as Targeting Agents for Nucleic Acids" 〃Metal Ions in Biological Systms〃 ed. by A. Sigel and H. Sigel, Marcel Dekker, Inc,. 33. 29-52 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Y. Inouye et. al: "Differential Contribution of Metal Complexation and Dimerization to the Chemotherapeutic Potential of Bicyclen-Zn2^<11> Complex against Human Immunodeficiency Virus" Biol. Pharm. Bull.19 (3). 456-458 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] T. Koike et. al: "Novel Properties of Cooperative Dinuclear Zinc (II) Ions : The Selective Recognition of Phosphmonoesters and Their P-O Ester Bond Cleavage by a New Dinuclear Zinc (II)" J. Am, Chem. Soc. 118 (13). 3091-3099 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] T. Koike et. al: "Bis (ZnII-Cyclen) Complex as a Novel Receptor of Barbiturates in Aqueous Solution." Chem. Europ. J.2 (6). 617-623 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] X. H. Bu et. al: "Stabilization of Nickel (III) ion by New Macrocyclic Dioxotetraamines Bearing Functional Pendant Donors" Polyhedron. 15. 161-163 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Y. Kodama et. al: "A New Cyclam with a Triphenylphosphine-pendant and its Metal Complexes" Inorg. Chem. Acta. 246. 151-158 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] T. Koike et. al: "Metalloenzyme Models that Answer Mysteries Surrounding the Intrinsic Properties of Zn^<II>" Comprehensive Supramoleculaar Chemistry 10. Pergamon. 429-444 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] E. Kimura: "Creation of new Supramoleculaar Sceince with Macrocyclic Polyamines" (1996 Pharmaceutical Society of Japan Award Review) Yakugaku Zasshi,. 116 (8). 587-605 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] H. Hashimoto et. al: "Hydrolysis of Lipophilic Esters Catalyzed by a Zinc (II) Complex of a Long Alkyl-Pendant Macrocyclic Tetraamine in Micellar Solution" J. Am. Chem. Soc.118 (45). 10963-10970 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] X. H. Bu et. al: "Synthesis, Crystal Structure and Properties of the Copper (II) Complex of a New Dioxocyclam Appeded with Two 8-Methylquinilines as Additional Donor Pendants" Inorg. Chim. Acta.249. 125-130 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] T. Koike et. al: "Intrinsic Properties of Zinc (II) Ion Pertient to Zinc Enzymes" Advance in Inorganic Chemistry, Ed. by A. G. Sykes, Academic Press,. 44. 229-261 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] T. Watanabe et al.: "A Novel Biomimetic Zinc (II) -Fluorophore, Dansylamin oethyl-Pendant Macrocyclic Tetraamine 1. 4, 7, 10-Tetraazacyclododecane (Cyclen)" J. Am. Chem. Soc.118 (50). 12696-12703 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] T. Koike et. al: "The Catalytic Carboxyester Hydrolysis by a New Zinc(II)Complex with an Alcohol-Pendant Cyclen. (1-(2-Hydroxyethy1)-1, 4, 7, 10-tetraazacyclododecane): A Novel Model for Indirect Activation of the Serine Nucleophile by Zinc(II)in Zine Enzymes" J. Am. Chem. Soc.117. 1210-1219 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] M. Kodama et. al: "Complexation Reaction of Aluminium Ions with Polymine Polycarboxylic Macrocycles in an Aqueous Solution" Bull. Chem. Soc. Jpn.68. 852-857 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] E. Kimura et. al: "Molecular Recognition of Terephthalic Acid by Supramolecular Self-Assembly of an Acridine-Pendant Cyclen-Zn(II)Complex" Angew. Chem. Int. Ed. Engl.34. 663-664 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] M. Kodama et. al: "Formation Equilibrium of a Copper(II)-Binuclear Complex of a New Pyridyl-Containing Tetraoxo Octaaza Macrocyclic Ligand Ligand and Its Polarographic Reduction Behavior" Bull. Chem. Soc. Jpn.68. 1627-1633 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] X. H. Bu et. al: "New 1, 4, 7, 10-Tetraazacyclotridecane-11, 13-dione Ligands Appended with Additional Donor(s)8-Methylquinoline(s): Crystal Structures and Cheracterization of Their Copper(II)Complexes" J. Chem. Soc. Dalton Trans.2289-2295 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] James H. R. Tucker et. al: "A Zinc(II)-Cyclen Complex Attached to an Anthraquinone Moiety that Acts as a Redox-Active Nucleobase Receptor in Aqueous Solution" Bull. Chem. Soc. Jpn.68. 2465-2469 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] K. Kobayashi et. al: "Molecular Structure of Chloro-[(25, 55, 85, 115)-2, 5, 7, 8,11-tetraethyl-1, 4, 7, 10-tetraazacyclododecane]Zinc(II)Perchlorate" Analytical Science. 11. 1029-1030 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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