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Development of new therapeutic reagents for trypanosoma disease based on the irreversible enzyme inhibition mechanism

Research Project

Project/Area Number 24651254
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Chemical biology
Research InstitutionHokkaido University

Principal Investigator

NISHIMURA Shinichiro  北海道大学, 先端生命科学研究科(研究院), 教授 (00183898)

Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
KeywordsChargas' disease / Trypanosoma cruzi / sialydase / inhibitor / suicide substrate / nanoparticle / nanomedicine / トリパノソーマ症 / トランスシアリダーゼ / 非可逆的阻害剤 / ナノ微粒子 / 量子ドット / 感染症治療薬 / 阻害剤 / 自殺基質 / イメージング
Research Abstract

Cardiopathy caused by the protozoan Trypanosoma cruzi, the etiologic agent of Chargas' disease, is the main cause of death in endemic regions of Latin America. Since nifurtimox and benznidazole are approved as therapeutic reagents for this disease, the efficacy is limited and serious side effects and toxicity were reported. Therefore, advent of novel therapeutic reagents has been strongly required.
We have discovered by collaborative research with a team at University of Rio de Janeiro that some suicide substrate-based derivatives of sialidases become a new class of leads toward drugs for the treatment of infectious diseases related to the Chargas' disease. In the present study, we aimed to establish for the general protocol for the assembling suicide substrate-based derivatives on the surface of nanoparticles that can convert into practically promising level of therapeutic reagents candidates as "nanomedicine".

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (9 results)

All 2014 2013 2012

All Journal Article (8 results) (of which Peer Reviewed: 8 results) Presentation (1 results) (of which Invited: 1 results)

  • [Journal Article] Synthesis of neoglycosphingolipids from methoxyamino-functionalized ceramide2014

    • Author(s)
      Junya Ishida, Hiroshi Hinou, Kentaro Naruchi, Shin-Ichiro Nishimura
    • Journal Title

      Bioorganic Medicianl Chemistry Letters

      Volume: 24 Issue: 4 Pages: 1197-1200

    • DOI

      10.1016/j.bmcl.2013.12.091

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] A New Approach for the Synthesis of Hyper-Branched N-Glycan Core Structures from Locust Bean Gum2013

    • Author(s)
      H. V. Ravi Kumar, Kentaro Naruchi, Risho Miyoshi, Hiroshi Hinou, Shin-Ichiro Nishimura
    • Journal Title

      Organic Letters

      Volume: 15 Issue: 24 Pages: 6278-6281

    • DOI

      10.1021/ol403140h

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Attomolar-level Detection of Influenza A Virus Hemagglutinin Human H1 and Avian H5 Using Glycan-blotted Field Effect Transistor Biosensor2013

    • Author(s)
      Sho Hideshima, Hiroshi Hinou, Daisuke Ebihara, Ryosuke Sato, Shigeki Kuroiwa, Takuya Nakanishi, Shin-Ichiro Nishimura, Tetsuya Osaka
    • Journal Title

      Analytical Chemistry

      Volume: 85 Issue: 12 Pages: 5641-5644

    • DOI

      10.1021/ac401085c

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Fluorescence polarization-based assay using N-glycan-conjugated quantum dots for screening in hemagglutinin blockers for influenza A viruses2013

    • Author(s)
      Okamatsu M, Feng F, Ohyanagi T, Nagahori N, Someya K, Sakoda Y, Miura N, Nishimura S, Kida H
    • Journal Title

      J Virol Methods

      Volume: 187 Issue: 2 Pages: 390-394

    • DOI

      10.1016/j.jviromet.2012.11.004

    • NAID

      120005228377

    • Related Report
      2013 Annual Research Report 2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Macrocyclic Mechanism-based Inhibitor for Neuraminidases2013

    • Author(s)
      Hirokazu Kai, Hiroshi Hinou, Kentaro Naruchi, Takahiko Matsushita, and Shin-Ichiro Nishimura
    • Journal Title

      Chemistry : A European Journal

      Volume: 19 Issue: 4 Pages: 1364-1372

    • DOI

      10.1002/chem.201200859

    • Related Report
      2013 Annual Research Report 2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Novel thiosialosides tethered to metal nanoparticles as potent influenza A virus hemagglutinin blockers2013

    • Author(s)
      Feng F., Sakoda Y., Ohyanagi T., Nagahori N., Shibuya H., Okamastu M., Miura N., Kida H., Nishimura S-I.
    • Journal Title

      Antivir. Chem. Chemoth.

      Volume: 23 Pages: 59-65

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Aglycone-focused randomization of 2-difluoromethylphenylsialoside-type suicide substrates for neuraminidases2012

    • Author(s)
      Hirokazu Kai, Hiroshi Hinou, Shin-Ichiro Nishimura
    • Journal Title

      Bioorganic & Medicinal Chemistry

      Volume: 20 Issue: 8 Pages: 2739-2746

    • DOI

      10.1016/j.bmc.2012.02.001

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Glycomics for drug discovery: Metabolic perturbation in androgen-independent prostate cancer cells induced by unnatural hexosamine mimics2012

    • Author(s)
      Nishimura S-I., Hato M., Hyugaji S., Feng F., and Amano M.
    • Journal Title

      Angew. Chem. Int. Ed.

      Volume: 51 Issue: 14 Pages: 3386-3390

    • DOI

      10.1002/anie.201108742

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] Glycomics and Drug Discovery2012

    • Author(s)
      西村紳一郎
    • Organizer
      26th International Carbohydrate Symposium
    • Place of Presentation
      Hotel Melia Castilla (Spain)
    • Related Report
      2012 Research-status Report
    • Invited

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Published: 2013-05-31   Modified: 2019-07-29  

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