1996 Fiscal Year Annual Research Report

生体金属による遺伝子発現制御

Research Project

Project/Area Number	08249103
Research Category	Grant-in-Aid for Scientific Research on Priority Areas
Research Institution	Hiroshima University
Principal Investigator	木村榮一広島大学, 医学部, 教授 (30034010)
Co-Investigator(Kenkyū-buntansha)	塩谷光彦岡崎国立共同研究機構, 分子科学研究所, 教授 (60187333) 杉浦幸雄京都大学, 化学研究所, 教授 (40025698)
Keywords	大環状ポリアミン / 抗HIV活性 / 亜鉛錯体 / 亜鉛フィンガー / 塩基配列認識 / 遺伝子プロモーター領域 / TATAボックス / DNA融解温度
Research Abstract	木村,榮一(広島大学医学部) 1.大環状ポリアミンの亜鉛錯体が、抗HIV活性を有することを見い出した。殊に、Biscyclen-Zn_2^<II>錯体は、抗HIV活性が(in vitro test)が極めて強く、或いは、次世代の抗エイズ薬の候補となりうることを示した。 2.Zn-Cyclen錯体は、核酸塩基中にイミド基をもつチミン、ウラシルをpH水溶液中選択的に認識、捕捉することを我々は発見したが(例:J.Am.Chem. Soc.,115,6730-6737(1993))、polyT(polyU)においても同様に結合し、polyT-polyAのdouble strandを効果的に解離させることを発見した。杉浦幸雄(京都大学化学研究所) 3.一般に、タンパク質とDNAとの位置関係を決定する上で重要であるのがバックボーンりん酸とのコンタクトである、それ故、このよく保存された塩基性アミノ酸残基を中心にバックボーンりん酸とコンタクトするアミノ酸残基に着目し、3個の亜鉛フィンガーを有するSplのDNA認識における各亜鉛フィンガーの独立性について考察した。 Splの場合には、亜鉛フィンガー2,3がコンタクトすると考えられる領域では、バックボーンりん酸とのコンタクトがG鎖に片寄っているが、フィンガー1がコンタクトすると考えられる領域では、GとCの両鎖にわたり幅広く認められる。また、別の実験結果から1つの亜鉛フィンガー内での変異が、他の亜鉛フィンガーの塩基配列特異性に影響を及ぼすことが判明した。塩谷光彦(岡崎国立共同研究機構分子科学研究所) 4.遺伝子プロモーター領域のATクラスター部位を融解する金属錯体の合成:チミン塩基に選択的に結合する亜鉛錯体が、ウイスルDNAの転写領域に存在するTATAboxを含む19merDNAの二本鎖構造を不安定化し、その融解温度を低下させることを見出した。これは亜鉛錯体特有のもので、銅錯体やニッケル錯体の場合には、逆に融解温度を上昇させた。

Research Products

(17 results)

All Other

All Publications (17 results)

[Publications] H. Fujioka et. al.: "A new Bis (Zinc (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 Systems" 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^<II> 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 Phosphomonoesters and Their P-O Ester Bond Cleavage by a New Dinuclear Zinc (II) Cryptate" J. Am. Chem. Soc. 118. 3091-3099 (1996)
[Publications] T. Koike et. al: "Bis (Zn^<II>-Cyclen) Complex as a Novel Receptor of Barbiturates in Aqueous Solution." Chem. Europ. J. 2. 617-623 (1996)
[Publications] X. H. Bu et.al: "Stabilization of Nickel (III) ion by New Macrocyclic Diozotetraamines 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. Chim. Acta.246. 151-158 (1996)
[Publications] T. Koike et. al: "Metalloenzyme Models that Answer Mysteries Surrounding the Intrinsic Properties of Zn" Comprehensive Supramoleculaar Chemistry' 10, Pergamon. 429-444 (1996)
[Publications] E. Kimura: "Creation of new Supramoleculaar Science with Macrocyclic Polyamines" (1996 Pharmaceutical Society of Japan Award Review) Yakugaku Zasshi. 116. 587-605 (1996)
[Publications] H. Hashimoto et. al: "Hydrolysis of Lipophilic Esters Catalyzed by a Zinc (II) Complex of a Long Alkyl-Pendant Macrocyclic Teraamine in Micellar Solution" J. Am. Chem. Soc.118. 10963-10970 (1996)
[Publications] X. H. Bu et. al: "Synthesis, Crystal Structure and Properties of the Copper (II) Complex of a New Dioxocyclam Appended with Two 8-Methylquinolines as Additional Donor Pendants" Inorg. Chim. Acta.249. 125-130 (1996)
[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)
[Publications] T. Watanabe: "A Novel Biomimetic Zinc (II)-Fluorophore, Dansylamin oethyl-Pendant Macrocyclic Tetraamine 1, 4, 7, 10-Tetraazacyclododecane (Cyclen)" J. Am. Chem. Soc.118. 12696-12730 (1996)
[Publications] S. Aoki et. al: "A This (Zinc (II) -1. 4. 7. 10-Cecraazacyclododecane) Complex as a New Receptor for Phosphate Dianions in Aqueous Solution" J. Am. Chem. Soc.119(in press). (1997)
[Publications] M. Shionoya 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)
[Publications] M. Shionoya et. al: "Macrocyclic Metal Complexes for Selective Recognition of Nucleic Acid Bases and Manipulation of Gene Expression." Pure & Appl. chem.(in press).
[Publications] Y. Sugiura et. al: "Distinct Phosphate Backbone Contacts revealed by Some Mutant Peptides of Zinc Finger Protein Sp1 : Effect of Protein-Induced Bending on DNA Recognition" Biochemistry. 35. 8761-8768 (1996)

1996 Fiscal Year Annual Research Report

生体金属による遺伝子発現制御

Principal Investigator

木村 榮一 広島大学, 医学部, 教授 (30034010)

Research Products

[Publications] H. Fujioka et. al.: "A new Bis (Zinc (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 Systems" 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^<II> 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 Phosphomonoesters and Their P-O Ester Bond Cleavage by a New Dinuclear Zinc (II) Cryptate" J. Am. Chem. Soc. 118. 3091-3099 (1996)

[Publications] T. Koike et. al: "Bis (Zn^<II>-Cyclen) Complex as a Novel Receptor of Barbiturates in Aqueous Solution." Chem. Europ. J. 2. 617-623 (1996)

[Publications] X. H. Bu et.al: "Stabilization of Nickel (III) ion by New Macrocyclic Diozotetraamines 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. Chim. Acta.246. 151-158 (1996)

[Publications] T. Koike et. al: "Metalloenzyme Models that Answer Mysteries Surrounding the Intrinsic Properties of Zn" Comprehensive Supramoleculaar Chemistry' 10, Pergamon. 429-444 (1996)

[Publications] E. Kimura: "Creation of new Supramoleculaar Science with Macrocyclic Polyamines" (1996 Pharmaceutical Society of Japan Award Review) Yakugaku Zasshi. 116. 587-605 (1996)

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

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

[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)

[Publications] T. Watanabe: "A Novel Biomimetic Zinc (II)-Fluorophore, Dansylamin oethyl-Pendant Macrocyclic Tetraamine 1, 4, 7, 10-Tetraazacyclododecane (Cyclen)" J. Am. Chem. Soc.118. 12696-12730 (1996)

[Publications] S. Aoki et. al: "A This (Zinc (II) -1. 4. 7. 10-Cecraazacyclododecane) Complex as a New Receptor for Phosphate Dianions in Aqueous Solution" J. Am. Chem. Soc.119(in press). (1997)

[Publications] M. Shionoya 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)

[Publications] M. Shionoya et. al: "Macrocyclic Metal Complexes for Selective Recognition of Nucleic Acid Bases and Manipulation of Gene Expression." Pure & Appl. chem.(in press).

[Publications] Y. Sugiura et. al: "Distinct Phosphate Backbone Contacts revealed by Some Mutant Peptides of Zinc Finger Protein Sp1 : Effect of Protein-Induced Bending on DNA Recognition" Biochemistry. 35. 8761-8768 (1996)

木村榮一広島大学, 医学部, 教授 (30034010)