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Molecular structure-based study on the affinity of Clostridium producing toxins to human cell surface glycolipids

Research Project

Project/Area Number 18K05469
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 38040:Bioorganic chemistry-related
Research InstitutionNational Institute of Advanced Industrial Science and Technology

Principal Investigator

UZAWA Hirotaka  国立研究開発法人産業技術総合研究所, 材料・化学領域, 主任研究員 (60356566)

Co-Investigator(Kenkyū-buntansha) 平塚 淳典  国立研究開発法人産業技術総合研究所, 材料・化学領域, 副部門長 (70392652)
Project Period (FY) 2018-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords糖脂質 / 合成 / ガングリオシド / 検知チップ / 相互作用解析 / 毒素 / 相互作用 / ケモエンザイム合成 / 固定化 / リガンド / 細菌性毒素 / 認識 / ライブラリー
Outline of Final Research Achievements

Synthetic glycolipids having lipoic amides at the sphingosine parts were prepared by a chemo-enzymatic method. The glycolipids were installed onto Au surface on electrodes by a self-assembled monolayer (SAM) technique in a differential quartz crystal microbalance (QCM) biosensor for application in the binding analysis of Clostridium toxins (BTXs). The QCM analysis has disclosed that a certain type of BTXs binds a simple glycolipid (Lac-Cer) without sialic acids at the non-reducing end. This finding provides an important insight into the molecular recognition of these biological toxins for human cell surface glycolipids which has been a matter of controverse in relevant biochemical studies for a long time.

Academic Significance and Societal Importance of the Research Achievements

ボツリヌス毒素(BTX)は、神経細胞に存在する糖脂質に結合して致死的な中毒症状を示すタンパク質性生物毒素である。従来の報告では、糖脂質GT1bにBTX/Aが結合するが、生理学的条件下では結合しない等相反する結果が報告されている。これは、古典的な結合評価法が用いられている事、統一された手法で解析されていない事や組成の異なるBTXが用いられた事による。本研究では、単一分子量のBTXを用い、先端的センシング技術により再評価することで、報告例のない結合相互作用を解明する等、学術的新規性を見出した。得られた知見を高感度毒素検知法の開発に適用する事で、生物化学剤による犯罪防止に有効に資すると期待される。

Report

(8 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Products Report
  • Research Products

    (7 results)

All 2024 2023 2021 2020 2019

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (2 results) (of which Int'l Joint Research: 1 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Novel Glycolipid Chips with a Double Layer of Au Nanoparticles for Biological Toxin Detection2023

    • Author(s)
      Uzawa Hirotaka、Nagatsuka Takehiro、Seto Yasuo、Nishida Yoshihiro、Saito Masato、Tamiya Eiichi
    • Journal Title

      ACS Omega

      Volume: 8 Issue: 15 Pages: 13754-13762

    • DOI

      10.1021/acsomega.2c07976

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Assembly of Glycochips with Mammalian GSLs Mimetics toward the On-site Detection of Biological Toxins2021

    • Author(s)
      Uzawa Hirotaka、Kondo Satoshi、Nagatsuka Takehiro、Miyaguchi Hajime、Seto Yasuo、Oshita Aguri、Dohi Hirofumi、Nishida Yoshihiro、Saito Masato、Tamiya Eiichi
    • Journal Title

      ACS Omega

      Volume: 6 Issue: 48 Pages: 32597-32606

    • DOI

      10.1021/acsomega.1c04154

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Silicon nitride sugar chips for detection of Ricinus communis proteins and Escherichia coli O157 Shiga toxins2019

    • Author(s)
      Daiki Tanaka, Hirotaka Uzawa, Takehiro Nagatsuka, Yuki Oba, Atsunori Hiratsuka, Ken-ichi Tayama, Toshio Yoshida, Yasuo Seto, Hirofumi Dohi, Yoshihiro Nishida
    • Journal Title

      Analytical Biochemistry

      Volume: 580 Pages: 42-48

    • DOI

      10.1016/j.ab.2019.06.002

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] Silicon Nitride Chips Modified with Gb3 Trisaccharide for Rapid Detection of Verotoxins2019

    • Author(s)
      Hirotaka Uzawa, Atsunori Hiratsuka, Yasuo Seto, Ken-ichi Tayama, Toshio Yoshida, Yoshihiro Nishida
    • Organizer
      10th International Conference on Molecular Electronics and Bioelectronics (M&BE10)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] ケモエンザイム法による糖脂質ライブラリーの構築2019

    • Author(s)
      鵜沢浩隆、平塚淳典
    • Organizer
      第18回 産総研・産技連 LS-BT合同研究発表会
    • Related Report
      2019 Research-status Report
  • [Patent(Industrial Property Rights)] 非特異的吸着抑制効果の高い糖鎖リガンド、および該糖鎖リガンドを固定化した毒素検知チップ2024

    • Inventor(s)
      鵜沢 浩隆
    • Industrial Property Rights Holder
      国立研究開発法人産業技術総合研究所
    • Industrial Property Rights Type
      特許
    • Acquisition Date
      2024
    • Related Report
      Products Report
  • [Patent(Industrial Property Rights)] 非特異的吸着抑制効果の高い糖鎖リガンド、および該糖鎖リガンドを固定化した毒素検知チップ2020

    • Inventor(s)
      鵜沢浩隆
    • Industrial Property Rights Holder
      国立研究開発法人 産業技術総合研究所
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2020-071741
    • Filing Date
      2020
    • Related Report
      2020 Research-status Report

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Published: 2018-04-23   Modified: 2025-03-27  

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