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Crystal Structural Analysis of IL6/IL6 receptor Complex and Development of Functional Regulation of IL6 with cDNA

Crystal Structural Analysis of IL6/IL6 receptor Complex and Development of Functional Regulation of IL6 with cDNA
IL6/IL6 受体复合物的晶体结构分析及 cDNA 对 IL6 功能调节的开发
批准号:
13359003
负责人:
TSUKIHARA Tomitake
金额:
$31.78万
依托单位:
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (A)
财政年份:
2001
资助国家:
日本
项目状态:
已结题
起止时间:
2001 至 2002

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项目成果

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中文摘要
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英文摘要
1. Atotal of 150 mg AUK18l 6 was purified from 30 ml of abdominal dropsy. Sil6 receptor affinity column was prepared by using AUK181 6. 6 mg of Sil6 receptor was purified from CHO cells producing Sil6 receptor.2. Structure of IL 6 in the novel crystal form was determined at 2.3 A resolution. The crystal shucture showed a loop structure that is not visible in the crystal structure previously determined. This loop interacts probably with IL6 receptor.3. Inhibition of IL6 by a FELRY peptide that bind to IL6 was inspected. The FELRY at 0.2 to 25 % saturation was added to IL6 dependent cells under rIL6 stimulation. Significant suppression of cell growth was not detected. Other soluble peptides are in under inspection.4. The method for molecular observation by AFM was developed to analyze recognition among IL6, IL6 receptor and gp130.
期刊论文(15)
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Mizushima, T., Tsukihara, T: "The proteasome as a drug target"In: Kubinyi, II., Folkers, G., Mannhold, R., eds. Methods and Principles in Medicinal Chemistry. Wiley-VCH in press. (2003)
Mizushima, T.、Tsukihara, T:“蛋白酶体作为药物靶点”见:Kubinyi, II.、Folkers, G.、Mannhold, R.,编辑。
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Gejima, R, Tanaka, K, Nakashima, T, Hashiguchi, S, Ito, Y, Yoizaki, K, Sugimura, K: "Human single-chain Fv (scFv) antib ody spedfic to human IL-6 with the inhibitory activity on IL-6-signaling"Human Antibodies. 11. 121-129 (2002)
Gejima, R, Tanaka, K, Nakashima, T, Hashiguchi, S, Ito, Y, Yoizaki, K, Sugimura, K:“针对人 IL-6 的人单链 Fv (scFv) 抗体,对人 IL-6 具有抑制活性
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Nishimoto N, et al.: "Toxicity, pharmacokinetics, and dose finding study of repetitive treatment with humanized anti-interleukin 6 receptor antibody, MRA, in rheumatoid arthritis -a phase I/ll clinical study of MRA for rheumatoid arthritis in Japan"J. Rhe
Nishimoto N 等人:“人源化抗白细胞介素 6 受体抗体 MRA 重复治疗类风湿性关节炎的毒性、药代动力学和剂量探索研究 - 日本 MRA 治疗类风湿性关节炎的 I/II 期临床研究”J
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12
    X-ray crystallographic studies of intr- and inter-cellular transport
    • 批准号:
      21227003
    • 项目类别:
      Grant-in-Aid for Scientific Research (S)
    • 资助金额:
      $150.51万
    • 财政年份:
      2009
    • 负责人:
      TSUKIHARA Tomitake
    • 依托单位:
    Crystal structural analysis of connexin-26 gap junction channel to elucidate functional mechanism of gap junction
    Functional Mechanism and Structural Organization of Biological Macromolecular Assemblies
    • 批准号:
      16087101
    • 项目类别:
      Grant-in-Aid for Scientific Research on Priority Areas
    • 资助金额:
      $31.3万
    • 财政年份:
      2004
    • 负责人:
      TSUKIHARA Tomitake
    • 依托单位:
    High resolution X-ray crystal structural analysis of biological macromolecular assemblies
    • 批准号:
      16087206
    • 项目类别:
      Grant-in-Aid for Scientific Research on Priority Areas
    • 资助金额:
      $125.63万
    • 财政年份:
      2004
    • 负责人:
      TSUKIHARA Tomitake
    • 依托单位: