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A Novel Artificial Enzyme for In Vivo Free Radical Elimination

Research Project

Project/Area Number 14380409
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Biomedical engineering/Biological material science
Research InstitutionTokyo Metropolitan University

Principal Investigator

KAWAKAMI Hiroyoshi  Tbkyo Metropolitan University, Dept. of Applied Chemistry, Associate Professor, 工学研究科, 助教授 (10221897)

Co-Investigator(Kenkyū-buntansha) NAGAOKA Shoji  Tokyo Metropolitan University, Dept. of Applied Chemistry, Professor, 工学研究科, 教授 (30254147)
KUBOTA Sunao  St. Marianna University, School of Medicine, Professor, 第一外科, 教授 (20075500)
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥10,300,000 (Direct Cost: ¥10,300,000)
Fiscal Year 2004: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2003: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2002: ¥5,300,000 (Direct Cost: ¥5,300,000)
KeywordsMetallonornhyrin / Artificial Enzyme / Nanocarrier / Ischemia / reperfusion / Anticancer Drug / Antioxydant Drug / 糖鎖 / 虚血再潅流 / SOD活性 / ミトコンドリア / In vivo評価 / 活性酸素
Research Abstract

Reactive oxygen species (ROS^1) are considered to be implicated in the pathogenesis of a number of diseases, such as atherosclerosis, cancer, and Alzheimer's disease. Their toxic effects are amplified by pathological events including neutrophil activation, hyperoxia, metabolism of redox-active drugs, radiation exposure, and ischemia/reperfusion. Subsequently, the overproduced ROS,'such as superoxide radical anion (O_2^<.->), cause the membrane damage resulting from lipid peroxidation, as well as the attack on proteins and nucleic acids. Therefore, antioxidant enzymes are useful for the therapy of ROS-mediated injuries and diseases. We have synthesized a macromolecular Mn-porphyrin for enhancing half-life in the blood circulation. However, these Mn-porphyrins lack the ability to target the cells overproducing O_2^<.->, although the selective delivery of SOD mimics into every particular cell is promising for a radical approach to various therapy
In this study, we have synthesized a new SOD mimic to eliminate in vivo free radicals. We have synthyesized novel metalloporphyrin derivatives as SOD mimics. In addition, we have demonstrated the anticancer effects of metalloporphyrin derivatives with SOD activity. Finally, I have synthesized novel drug carriers containing metalloporphyrin derivatives as SOD mimics.

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (8 results)

All 2004 Other

All Journal Article (4 results) Publications (4 results)

  • [Journal Article] Liposomal Surface-Loading of Water-Soluble Cationic Iron(III) Porphyrins as Anticancer Drugs2004

    • Author(s)
      M.Yuasa, K.Oyaizu, A.Horiuchi, A.Ogata, T.Hatsugai, A.Yamaguchi, H.Kawakami
    • Journal Title

      Mol.Pharma. 1

      Pages: 387-389

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Design of metalloporphyrin- carbohydrate conjugates for a new SOD mimic with cellular recognition2004

    • Author(s)
      Shoichiro ASAYAMA, Eri KAWAMURA, Shoji NAGAOKA, Hiroyoshi KAWAKAMI
    • Journal Title

      Bioconjugate Chem. 15

      Pages: 1360-1363

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Liposomal Surface-Loading of Water-Soluble Cationic lron(III)Porphyrins as Anticancer Drugs2004

    • Author(s)
      M.Yuasa, K.Oyaizu, A.Horiuchi, A.Ogata, T.Hatsugai, A.Yamaguchi, H.Kawakami
    • Journal Title

      Mol. Pharma Vol.1

      Pages: 387-389

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Design of metalloporphyrin- carbohydrate conjugates for a new SOD mimic with cellular recognition2004

    • Author(s)
      S.Asayama, E.Kawamura, S.Nagaoka, H.Kawakami
    • Journal Title

      Bioconjugate Chem. Vol.15

      Pages: 1360-1363

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] S.ASAYAMA, T.MORI, S.NAGAOKA, H.KAWAKAMI: "Chemical Modification of Manganese Porphyrins with Biomolecules for New Functional Antioxidants"Journal of Biomaterials Science, Polymer Edition. Vol.14,No.11. 1169-1179 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] S.ASAYAMA, E.KAWAMURA, S.NAGAOKA, H.KAWAKAMI: "Application of Manganese Porphyrins with Superoxide Dismutase Activity to Antimetastatic Agent"Porphyrins. Vol.12,No.3-4. 103-106 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 川上浩良: "抗癌効果を有する新規SODミメティック金属ポルフィリンの開発"ファインケミカル(シーエムシー出版). Vol.32. 5-11 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] H.Kawakami, S.Nagaoka, S.Kubota: "Selective Cell Death by Water-Soluble Fe-Porphyrins with Superoxide Dismutase (SOD) Activity"Journal of Inorganic Biochemistry. 91. 349-355 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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