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Chemical modification of Profein Drugs with Polyethylene Glycol

Research Project

Project/Area Number 17500319
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biomedical engineering/Biological material science
Research InstitutionToin University of Yokohama

Principal Investigator

YOH Kodera  Toin University of Yokohama, Department of Life and Environmenatal Science, Associate Professor (80205426)

Co-Investigator(Kenkyū-buntansha) NISHIMURA Hiroyuki  Toin University of Yokohama, Department of Life and Environmenatal Science, Professor (60189313)
Project Period (FY) 2005 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,350,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥150,000)
Fiscal Year 2007: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2006: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2005: ¥1,500,000 (Direct Cost: ¥1,500,000)
KeywordsEnzyme / Biomaterial / Protein / Chemical modification / Metabolism / Clearance time / タンパク質の化学修飾 / ポリエチレングリコール / スーパーオキシドジスムターゼ / コラーゲン関節炎
Research Abstract

The target of this project is, 1) Chemical modification of protein drugs with a series of synthetic macromolecule, polyethylene gycol, 2) and to change their original characteristics, such as prolongation of blood circulation life-times, reduction of immune response, inducing immune tolerance, and increasing biological affinity of synthetic or allogenic protein drugs.
An anti-inflammatory enzyme, manganese-type superoxide dismutase was coupled with single-chained and double-chained polyethylene glycol derivatives (PEG). Especially, a branched PEG derivative with cyanuric acid as a spacer seems to be a best choice for prolongation of blood circulating life-time. Inflammatory activity of PEG-superoxide dismutase was checked in collagen-induced arthritis as well as reumatoid arthritis using DAB/1 and SKG mice, respectively.
Phenylalanine ammonia-lyase was also coupled with PEG derivatives, but another type of branced PEG derivatives was needed due to the enzymic stability. We have to synthesize various PEG derivatives with varied spacers.

Report

(4 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • Research Products

    (17 results)

All 2008 2007 2006 2005

All Journal Article (12 results) (of which Peer Reviewed: 4 results) Presentation (5 results)

  • [Journal Article] Poly(ethylene glycol)-modified Mn-SOD for prolonging its half-life in blood circulation2008

    • Author(s)
      羽田 宜弘, 他
    • Journal Title

      材料技術 26

      Pages: 18-21

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Poly(ethlene glycol)-modified Mn-SOD for prolonging its half-life in blood circulation2008

    • Author(s)
      Y Hada, M Takahashi, H Nishimura, Y Kodera, N Kawashima
    • Journal Title

      Material Technology 26

      Pages: 18-21

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Poly(ethylene glycol)-modified Mn-SOD for prolonging its half-life in blood circulation.2008

    • Author(s)
      羽田宜弘, 他
    • Journal Title

      材料技術 26

      Pages: 18-21

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genetic control of the spontaneous activation of CD4^+ Th cells in systemic lupus erythematosus-prone(NZB x NZW) F_1 mice.2006

    • Author(s)
      T Fujii, K Ikeda, N Nishimura, J Tokei, K Mitsui, Y Kodera, Y Inada, Y Xiu, K Nakamura, T Shirai, S Hlrose, H Nishimura
    • Journal Title

      Genes and Immunity 7

      Pages: 647-654

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Genetic control of the spontaneous activation of CD4^+Th cells in systemic lupus erythematosus-prone(NZB x NZW)F_1 mice.2006

    • Author(s)
      Takuma Fujii 他
    • Journal Title

      Genes and Immunity 7

      Pages: 647-654

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Phenylalanine ammonia-lyase modified with polyethylene glycol:potential therapeutic agent for phenylketonuria2005

    • Author(s)
      K.Ikeda, 他
    • Journal Title

      Amino Acids 29

      Pages: 283-287

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Hyaluronidase:a new assay method and its inhibitors2005

    • Author(s)
      H.Nagata, 他
    • Journal Title

      Trans. Mater. Res. Soc. Jpn 30

      Pages: 421-424

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Phenylalanine ammonia-lyase modified with polyethylene glycol : potential therapeutic agent for phenylketonuria.2005

    • Author(s)
      K Ikeda, E Schiltz, T Fujii, M Takahashi, K Mitsui, Y Kodera, A Matsushima, Y Inada, GE Schulz, H Nishimura
    • Journal Title

      Amino Acids 29

      Pages: 283-287

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Hyaluronidase : a new assay method and its inhibitors.2005

    • Author(s)
      H Nagata
    • Journal Title

      Trans. Mater. Res. Soc. Jpn. 30

      Pages: 421-424

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Effects of polyethylene glycol-binding superoxide dismutase on collagen induced arthritis.2005

    • Author(s)
      A.Ochiai 他
    • Journal Title

      Modern Lheumatology vol 15

      Pages: 312-312

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Phenylalanine ammonia-lyase modified with polyethylene glycol : potential therapeutic agent for phenylketonuria.2005

    • Author(s)
      K.Ikeda 他
    • Journal Title

      Amino Acids vol 29

      Pages: 283-287

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Hyaluronidase : a new assay method and its inhibitors2005

    • Author(s)
      H.Nagata 他
    • Journal Title

      Trans.Mater.Res.Soc.Jpn vol 30

      Pages: 421-424

    • Related Report
      2005 Annual Research Report
  • [Presentation] Therapeutic effects of phenylalanine ammonia-lyase modified with polyethylene glycol on the mouse model of phenylketonuria.2007

    • Author(s)
      M Kodajima, K Ikeda, N Okada, A Kusano, K Mitsui, Y Kodera, A Matsushima, Y Inada, H Nishimura
    • Organizer
      Toin International Symposium on Biomedical Engineering
    • Place of Presentation
      Yokohama
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Polyethylene glycol modified enzymes alter the original characteristics2006

    • Author(s)
      Y.Kodera, 他
    • Organizer
      Toin International Symposium on Biomedical Engineering
    • Place of Presentation
      Yokohama
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Polyethylene glycol modified enzymes alter the original characteristics.2006

    • Author(s)
      Y Kodera, Y Hada, K Wakabayashi, H Nishimura, A Matsushima, A Inada, S Takahashi
    • Organizer
      Toin International Symposium on Biomedical Engineering
    • Place of Presentation
      Yokohama
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Effects of polyethylene glycol-binding superoxide dismutase on collagen induced arthritis.2005

    • Author(s)
      A Ochiai, H Matsuno, K Yoshida, M Goto, Y Kodera, K Sakurai, K Wakabayashi, K Yudoh, S Kano
    • Organizer
      14th Int. Rheumatology Symposium
    • Place of Presentation
      Yokohama
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Anti-inflammatory activity of chemically modified superoxide dismutase in collagen-induced arthritis model mice.2005

    • Author(s)
      K Wakabayashi, Y Hada, A Ochiai, H Matsuno, M Takahashi, H Nishimura, Y Kodera
    • Organizer
      78th Nihon Seika Gakkai
    • Place of Presentation
      Kobe
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2005-04-01   Modified: 2016-04-21  

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