1996 Fiscal Year Annual Research Report

核酸部位の選択的認識と遺伝子発現制御機能をもつ新規大環状化合物の創造

Research Project

Project/Area Number	07458144
Research Institution	HIROSHIMA UNIVERSITY
Principal Investigator	木村榮一広島大学, 医学部, 教授 (30034010)
Keywords	大環状ポリアミン / 二核亜鉛錯体 / 抗HIV活性 / 核酸塩基認識 / 神経毒ガス / 解毒 / 亜鉛蛍光試薬 / ダンシルペンダント
Research Abstract	1.大環状テトラアミンの金属錯体を適当でスペーサーでつなげた二核錯体を各種合成し、それらが強い抗HIV活性を有することを発見した。これらは、次世代の抗エイズ薬のリ-ド化合物として大きな展開が期待される。 2.上記錯体や、新たに合成された機能性ペンダントをもつ大環状化合物が水中、生理pHで、ポリヌクレオチド(1本鎖および2本鎖)中のチミンまたはウラシルを選択的に認識し、それらに強く結合すること、および2本鎖(polyU-polyA、poly (dT) -poly (dA) )を1本鎖に解離させることを融点(Tm)、UV測定法などで明らかにした。 3.脂溶性アルキル基を大環状テトラアミンにつけた新規亜鉛錯体を合成した。それが特に農薬や神経毒ガスサリンなどのリン酸トリエステルの最もすぐれた加水分解(解毒)触媒として働くことを見出した。 4.ダンシル基をペンダントにもつ新規大環状テトラアミンを合成。それが亜鉛選択的蛍光試薬として、極めてすぐれていることを発見した。細胞内微量亜鉛の蛍光分析に用いた。

Research Products
(14 results)

All Other

All Publications (14 results)

[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)
[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)
[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)
[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)
[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)
[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)
[Publications] X. H. Bu et. al: "Stabilization of Nickel (III) ion by New Macrocyclic Dioxotetraamines Bearing Functional Pendant Donors" Polyhedron. 15. 161-163 (1996)
[Publications] Y. Kodama et. al: "A New Cyclam with a Triphenylphosphine-pendant and its Metal Complexes" Inorg. Chem. Acta. 246. 151-158 (1996)
[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)
[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)
[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)
[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)
[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)
[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)

1996 Fiscal Year Annual Research Report

核酸部位の選択的認識と遺伝子発現制御機能をもつ新規大環状化合物の創造

Principal Investigator

木村 榮一 広島大学, 医学部, 教授 (30034010)

Research Products

[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)

[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)

[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)

[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)

[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)

[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)

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

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

[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)

[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)

[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)

[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)

[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)

[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)

木村榮一広島大学, 医学部, 教授 (30034010)