Design of peptide-containing chelate metal complexes for recognition of specific base sequences in DNA

用于识别 DNA 中特定碱基序列的含肽螯合金属配合物的设计

基本信息

  • 批准号:
    06640733
  • 负责人:
  • 金额:
    $ 1.15万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for General Scientific Research (C)
  • 财政年份:
    1994
  • 资助国家:
    日本
  • 起止时间:
    1994 至 1995
  • 项目状态:
    已结题

项目摘要

In order to evaluate the function of amino acid residues in the stereospecific binding of peptide-containing chelate complexes on DNA,the binding structures of various amino acid and peptide complexes of Cu (II) were investigated by DNA-fiber ESR spectroscopy and it was revealed that the orientation of the coordination plane of the complexes could be regulated by an appropriate choice of the amino acid and the sequence in the peptides. It was also found by means of acrylamide gel electrophoresis that some histidine-containing peptide complexes recognize differently the DNA base sequence from other peptide complexes in the DNA scission reaction with hydrogen peroxide. The research on the structure or the binding constant for various Cu (II) complexes of cationic water soluble porphyrins and Schiff bases were also published.The investigation was further extended over the phenanthroline Cu (II) complexes. Various 2,9-or 5-substituted-1,10-phenanthroline, that are the intermediates for the combined peptide-chelate ligands, were synthesized and the function of the Cu (II) complexes in the interaction with DNA were assayd by the DNA-fiber ESR spectroscopy and by an agarose gel electrophoresis of the reaction products of phage DNA with hydrogen peroxide. It was revealed that the cleaving is active for the complexes randomly orienting on the DNA and for the ligands with more electron-withdrawing substituents such as NO2 or Cl. It was proposed that the non-intercalated species activate hydrogen peroxide and that the pKa value of the coordinated water molecules affect the reactivity. The binding structure of mixed chelate complex of 1,10-phenanthroline and leucine with Pt (II) on self-compliment oligonucleotide, GCGCAATTGCGC,was investigated by 2D-NMR and was found that this complex intercalate from the major groove at the AT base pair.
为了评价氨基酸残基在含肽螯合物与DNA立体特异性结合中的作用,利用DNA纤维ESR光谱研究了Cu (II)的各种氨基酸和肽配合物的结合结构,发现通过选择合适的氨基酸和肽序列可以调节配合物的配位面取向。通过丙烯酰胺凝胶电泳还发现,在与过氧化氢的DNA裂解反应中,一些含组氨酸的肽复合物与其他肽复合物对DNA碱基序列的识别不同。对阳离子水溶性卟啉和席夫碱的各种Cu (II)配合物的结构或结合常数的研究也有报道。对邻菲罗啉铜(II)配合物的研究进一步扩展。合成了多种2,9或5-取代-1,10-菲罗啉作为肽-螯合配体的中间体,并通过DNA纤维ESR光谱和噬菌体DNA与过氧化氢反应产物琼脂糖凝胶电泳分析了Cu (II)配合物与DNA相互作用的功能。结果表明,在DNA上随机取向的配合物和具有更多吸电子取代基的配体(如NO2或Cl)具有切割活性。结果表明,非插层物质激活过氧化氢,配位水分子的pKa值影响反应活性。利用二维核磁共振(2D-NMR)研究了1,10-菲罗啉-亮氨酸混合螯合物与Pt (II)在自补寡核苷酸GCGCAATTGCGC上的结合结构,发现该配合物从at碱基对的主槽插入。

项目成果

期刊论文数量(52)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
K.Sato,M.Chikira,Y.Fuji,A.Komatsu: "Stereospecific Binding of Chemically Modified Salen-type Schiff Base Compexes of Copper(II) with DNA [salen=bis(salicylidene)ethylene diamine]" J.Chem.Soc.,Chem.Commun.625-626 (1994)
K.Sato、M.Chikira、Y.Fuji、A.Komatsu:“化学修饰的铜 (II) Salen 型席夫碱络合物与 DNA 的立体特异性结合 [salen=双(水杨基)乙二胺]”J.Chem。
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    0
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M.Chikira,他7名: "ESR Stcly of Binding Structures of Cationic Water-soluble Metolls-porphyrins on the Highly Oriented DNA-fibres" J.Chem.Soc.,Dalton Transaction. (in press). (1995)
M. Chikira 和其他 7 人:“阳离子水溶性 Metolls-卟啉在高度定向 DNA 纤维上的结合结构的 ESR Stcly”,J.Chem.Soc.,Dalton Transaction(1995 年出版)。
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    0
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千喜良 誠: "DNA塩基配列特異性を認識するペプチド金属錯体の分子設計" 中央大学理工学研究所年報. 3(印刷中). (1996)
Makoto Chikira:“识别 DNA 序列特异性的肽金属复合物的分子设计”中央大学科学技术研究所年度报告 3(出版中)。
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M.Chikira: "Electron Spin Resonance Study of the Binding Structures of Cationic Water-soluble Metlloporphyrins on HIghly Oriented Deoxyribonucleic Acid Fibres" J.Chem.Soc.,Dalton Transaction. 1325-1331 (1995)
M.Chikira:“阳离子水溶性金属卟啉在高度定向脱氧核糖核酸纤维上的结合结构的电子自旋共振研究”J.Chem.Soc.,Dalton Transaction。
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M.Chikira: "Design of peptide-containing chelate metal complexes for specific recognition of base sequences in DNA" Annual.Rep.Inst.Sci.Eng.Chuo Univ.2. 43-47 (1995)
M.Chikira:“用于特异性识别 DNA 碱基序列的含肽螯合金属复合物的设计”Annual.Rep.Inst.Sci.Eng.Chuo Univ.2。
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CHIKIRA Makoto其他文献

CHIKIRA Makoto的其他文献

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{{ truncateString('CHIKIRA Makoto', 18)}}的其他基金

Synthesis and characterization of composite metal complexes aiming at regulations of genetic information
针对遗传信息调控的复合金属配合物的合成与表征
  • 批准号:
    21550070
  • 财政年份:
    2009
  • 资助金额:
    $ 1.15万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
DNA base recognition and reaction with polynuclear metal complexes
DNA碱基识别及与多核金属配合物的反应
  • 批准号:
    14540541
  • 财政年份:
    2002
  • 资助金额:
    $ 1.15万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Regulation of orientation and the dynamic behavior of metal complexes bound to DNA
与 DNA 结合的金属配合物的方向和动态行为的调节
  • 批准号:
    12640564
  • 财政年份:
    2000
  • 资助金额:
    $ 1.15万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Novel Binding Structures and Reactions of Metal Complexes of Some Combired Ligands
一些组合配体的金属配合物的新型结合结构和反应
  • 批准号:
    09640674
  • 财政年份:
    1997
  • 资助金额:
    $ 1.15万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
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