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Syntheses of Novel Biologically Active Compounds Utilizing Countesactive Action in diving Body and their Clinical Trials

Research Project

Project/Area Number 13672379
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 応用薬理学・医療系薬学
Research InstitutionAkita Unversity

Principal Investigator

SUZUKI Toshio  Akita Univ., School of Medecine, Professor, 医学部, 教授 (20108559)

Co-Investigator(Kenkyū-buntansha) ITOH Kunihiko  Akita Univ. School of Medicine, Associate Professor, 医学部, 助教授 (90221770)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2001: ¥1,300,000 (Direct Cost: ¥1,300,000)
Keywordsantedrug / Steroid / ear edema bioassay / granuloma bioassay / phage display method / human recombinant Fab / O157 / verotoxin / ヒト型リコンビナントFab / ヒト型抗体 / ファージディスプレイ
Research Abstract

Novel steroids, hemisuccinyl methyl glycolates were prepared from the corresponding methyl glycolates derived from predonisolone and dexamethasone based on a concept of the antedrug. Their topical anti-inflammatory activity was evaluated through croton-induced ear edema and paper disk granuloma bioassay. Two (20S)-succinyl dexamethasone derivatives indicated more potent anti-inflammatory activity than the parent compounds and did not show corticosteroidal side effects of thymic, adrenal involution or body weight loss due to easy conversion of the succinyl derivatives into active compounds followed by rapid elimination from the circulation system in the rat. From these results, these two derivatives might be candidates as the novel steroids without the systemic side effects of corticosteroids.
On the other hand, we tried to isolate the neutralizing human antibody against verotoxin (VT), which is an enterotoxin produced from Escherichia coli, O157-H7. We constructed human antibody combinatorial library from PBL of the O157-postinfected donor. We selected three VT1-reactive rFab clones and two VT2-reactive rFab clones from the antibody combinatorial antibody panning against VTs. These clones were found to be cross-reactive with another type of VT, and showed no neutralizing activity against VTs. These results suggest that isolated clones would recognize the neutralization-unrelated epitope commonly presented in both VT1 and VT2.

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] Toshio Suzuki: "Synthesis and Fate of Novel steroids, Hemisuccinyl Meth of Glycolates Based on the Concept of Antedeag"(submitted).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kunihiko Itoh: "Different Binding Property of Verotoxin-1 and Verotoxin-2 Against Their Glycolipid Receptor, Globotriaosylceramide"Tohoku J. Exp. Med. 195. 237-243 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kyoji Okada: "Enhanced Antitumor Effect of Ultrasound in the Presence of Piroxicam in a Mouse Air Pouch Model"Jpn. J. Cancer Res.. 93. 216-222 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kunihiko Itoh: "Phage Display Cloning and Characterization of Monoclonal Antibody Genes and Recombinant Fab Fragment against the CD98 Oncoprotein"Jpn. J. Cancer Res.. 92. 1313-1321 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kunihiko Itoh: "Methods in Molecalar Biology"P.M.O'Brien and R.Aitken. 401 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Toshio Suzuki: "Synthesis and Fate of Novel Steroid, Hemisuccinyl Methyl glycolates Based on the Concept of Antedrug"submitted.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kunihiko Itoh: "Different Birding Property of Verotoxin-1 and Verotoxin-2 Against their glycoliped Rcepter, Globotriaosylceramide"Tohoku G. Exp. Med.. 195. 237-243 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kyoji Okada: "Enhanced Antitumor Effect of Ultrasound in the presence of Piroxicam in a Muse Air Pouch Model"Jpn. J. Cancer Res. 93. 216-222 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kunihiko Itoh: "Phage Display Cloring and Characterization of Moroclonal Antibody Genes and Recombirant Fab Fragment Against the CD98 Oncoprotein"Jpn. J. Cancer Res.. 92. 1313-1321 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kunihiko Itoh: "Methods in Molecular Biology"P. M. O'Brien and R, Aitken. 401 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kunihiko Itoh: "Different Binding Property of Verotoxin-1 and Verotoxin-2 Against their glycolipid Receptor, Globotriaosylceramide"Tohoku J. Exp. Med.. 195. 237-243 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kyoji Okada: "Enhanced Antitumor Effect of Ultrasound in the Presence of Piroxicam in a Mouse Air Pouch Model"Jpn. J. Cancer Res.. 93. 216-222 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kunihiko Itoh: "Phage Display Cloning and Characterization of Monoclonal Antibody Genes and Recombinant Fab Fragment Against the CD98 Oncoprotein"Jpn. J. Cancer Res.. 92. 1313-1321 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kunihiko Itoh: "Methods in Molecular Biology"P. M. O'Brien and R. Aitken. 401 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Itoh K, Suzuki T, et al.: "Different binding property verotoxin-1 and verotoxin-2 against their qlycolipid receptor globotriaosylceramide"Tohoku J, Exp, Med. (in press). (2002)

    • Related Report
      2001 Annual Research Report

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

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