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NMR method to obtain structural fingerprints of an intact monoclonal antibody acquired under formulated storage conditions

Research Project

Project/Area Number 18K19415
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 47:Pharmaceutical sciences and related fields
Research InstitutionNational Institute of Advanced Industrial Science and Technology

Principal Investigator

Takeuchi Koh  国立研究開発法人産業技術総合研究所, 生命工学領域, 研究グループ長 (20581284)

Co-Investigator(Kenkyū-buntansha) 徳永 裕二  国立研究開発法人産業技術総合研究所, 生命工学領域, 研究員 (80713354)
Project Period (FY) 2018-06-29 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2018: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Keywords高分子バイオ医薬 / NMR / 創薬科学 / 高次構造解析 / バイオ医薬品 / 製剤条件 / 非破壊的 / 非侵襲的 / 測定技術開発 / バイオ医薬
Outline of Final Research Achievements

Non-invasive evaluation of tertiary structure is fundamental for the research, development, and use of the biologics. However, few methodologies are currently available for evaluating large molecular weight (MW) biologics, such as ther-apeutic monoclonal antibodies (mAbs; 150 kDa). Here, we have newly developed a 15N direct detection nuclear magnetic resonance (NMR) technique, the 15N direct detection CRINEPT, that allows the observation of the main chain amide reso-nances of a non-deuterated protein with MW 150 kDa. The technique not only substantially expands the range of pro-teins applicable to solution NMR studies, but also allows the non-invasive structural analyses of intact mAbs in a wide range of temperature and solvent conditions. As proof of principle, we successfully acquired the 15N-detected CRINEPT spectra of an intact mAb in its formulated solution at 4°C.

Academic Significance and Societal Importance of the Research Achievements

本研究では困難であった製剤・保存条件下での高分子バイオ医薬の高次構造評価を、独自のNMR技術:15N観測CRENEPT法の開発により可能にした。その際、代表的な高分子バイオ医薬である抗体について、完全に非破壊的な高次構造解析を低温かつ保存温度というNMR測定に不利な条件で実現することに成功した。本研究の成果は、バイオ医薬の高機能化を含む研究開発への貢献が期待されるが、本手法を用いることでNMR法により解析可能なタンパク質の数を飛躍的に向上させることが可能であるであるため、広く構造生命科学的研究に資するものである。

Report

(3 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • Research Products

    (3 results)

All 2020 2018

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

  • [Journal Article] Spotlight on the Ballet of Proteins: The Structural Dynamic Properties of Proteins Illuminated by Solution NMR2020

    • Author(s)
      Tokunaga Yuji、Viennet Thibault、Arthanari Haribabu、Takeuchi Koh
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 5 Pages: 1829-1829

    • DOI

      10.3390/ijms21051829

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Structural Fingerprints of an Intact Monoclonal Antibody Acquired under Formulated Storage Conditions via 15N Direct Detection Nuclear Magnetic Resonance2020

    • Author(s)
      Tokunaga Yuji、Takeuchi Koh、Okude Junya、Ori Kazutomo、Torizawa Takuya、Shimada Ichio
    • Journal Title

      Journal of Medicinal Chemistry

      Volume: - Issue: 10 Pages: 5360-5366

    • DOI

      10.1021/acs.jmedchem.0c00231

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 15N 直接検出NMR法による高分子量バイオ医薬の非侵襲的観測2018

    • Author(s)
      徳永 裕二,竹内 恒,鳥澤 拓也,奥出 順也,嶋田 一夫
    • Organizer
      第57回NMR討論会
    • Related Report
      2018 Research-status Report

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Published: 2018-07-25   Modified: 2021-02-19  

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