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

Research Project

Project/Area Number 13359003
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section展開研究
Research Field 広領域
Research InstitutionOsaka University

Principal Investigator

TSUKIHARA Tomitake  Institute for Protein Research, Professor, たんぱく質研究所, 教授 (00032277)

Co-Investigator(Kenkyū-buntansha) UEKI Tatzuo  Japan Synchrotron Radiation Research Institute, Directrate, 放射光研究所利用施設部門, 部門長(研究職)
YOSHIZAKI Kazuyuki  School of Health and Sport Science, Professor, 健康体育部, 教授 (90144485)
KAWAI Tomoji  Institute of Scientific and Industrial Research, Professor, 産業科学研究所, 教授 (20092546)
HIGUCHI Naohisa  Inter Cyto Nano Science CO., LTD, President, 代表取締役(研究職)
上坪 宏道  高輝度光科学研究センター, 副会長(研究職)
江島 大輔  味の素株式会社, 医薬研究所, 主任研究員
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥49,660,000 (Direct Cost: ¥38,200,000、Indirect Cost: ¥11,460,000)
Fiscal Year 2002: ¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2001: ¥31,850,000 (Direct Cost: ¥24,500,000、Indirect Cost: ¥7,350,000)
KeywordsIL6 / IL6 recetor / crvstal structure / AFM / signal transduction / インターロイキン-6 / インターロイキン-6受容体 / 複合体 / 結晶構造解析
Research Abstract

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.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] Choy EH, et al.: "Therapeutic benefit of blocking interleukin-6 activity with an anti-interleukin 6 receptor monoclonal antibody in rheumatoid arthritis : a randomized, double-blind, placebo-controlled, dose-escalation trial"Arthritis Rheum.. 46. 3143-3150 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 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. Rheum.. (in press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Gejima R, et al.: "Human single-chain Fv (scFv) antibody specific to human IL-6 with the inhibitory activity on IL-6-signaling"Human Antibody. 11. 121-129 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakahara H, et al.: "Anti-interleukin-6 receptor antibody therapy reduces vascular endotherlial growth factor (VEGF) production in rheumatoid arthritis"Arthritis Rheum.. (in press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mizushima, T., Tsukihara, T.: "The proteasome as a drug target"Methods and Principles in Medicinal Chemistry. (in press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Choy, EH, Isenberg, DA, Garrood, T, Farrow, S, Ioannon, Y, Bird, H, Cheung, N, Williams, B, Price, R, Yoshizaki, K, Nishimoto, N, Kishimoto, T: "Panay GS. Therapeutic benefit of blocking interleukin-6 activity with an anti-interleukin 6 receptor monoclonal antibody in rheumatoid arthritis: a randomized, double-blind, placebo-controlled, dose-escalation trial"Arthritis Rheum. 46. 3143-3150 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nishimoto, N, Yashizaki, K, Maeda, K, Kuritani, T, Deguchi, H, Sato, B, Imai, N, Kakehi, T, Takagi, N, Suemura, M, Kishimoto, T: "Toxicity, pharmacokinetics, and dose finding study of repeititve treahnent with humanized anti-interleukin 6 recs ptor antibody, MRA, in rheumatoid arthritis -a phase I/II clinical study of MRA for rheumatoid arthritis in Japan-"J. Rheum. in press. (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakahara, H: "Anti-interleukin-6 receptor antibody thera py reduces vascular endotherlial growth factor (VEGF) produ ction in rheumatoid arthritis"Arthritis Rheum. in press. (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Choy EH, et al.: "Therapeutic benefit of blocking interleukin-6 activity with an anti-interleukin 6 receptor monoclonal antibody in rheumatoid arthritis : a randomized, double-blind, placebo-controlled, dose-escalation trial"Arthritis Rheum.. 46. 3143-3150 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 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/II clinical study of MRA for rheumatoid arthritis in Japan"J.Rheum.. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Gejima R, et al.: "Human single-chain Fv (scFv) antibody specific to human IL-6 with the inhibitory activity on IL-6-signaling"Human Antibody. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nakahara H, et al.: "Anti-interleukin-6 receptor antibody therapy reduces vascular endotherlial growth factor (VEGF) production in rheumatoid arthritis"Arthritis Rheum.. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Mizushima T., Tsukihara T.: "The proteasome as a drug target"Methods and Principles in Medicinal Chemistry. (in press). (2003)

    • Related Report
      2002 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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