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Development of a gold nanoparticle-based approach to efficient small-molecule target identification

Research Project

Project/Area Number 18K05331
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 37020:Chemistry and chemical methodology of biomolecules-related
Research InstitutionTokyo University of Agriculture and Technology

Principal Investigator

Sakurai Kaori  東京農工大学, 工学(系)研究科(研究院), 准教授 (50447512)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywordsラベリング / 金ナノ粒子 / 化学プローブ / リガンド / 標的タンパク質探索
Outline of Final Research Achievements

The development of rational search and identification methods for target proteins is important for elucidating the mechanism of action of drugs and candidate compounds at the molecular level. Conventional methods for searching for target proteins have suffered from low search efficiency and substrate generality. In this study, we developed an efficient and selective protein labeling reaction by using gold nanoparticles as a probe substrate and utilizing their properties to address these problems. In addition, we have developed azide-modified gold-nanoparticles that enable the preparation of photoaffinity probes in a single step by click chemistry, and have realized a methodology to simplify target identification for natural products.

Academic Significance and Societal Importance of the Research Achievements

作用機序が明解で治療効果が高く副作用が少ない医薬品の開発に向けて、化合物の標的タンパク質とオフターゲットタンパク質、および標的経路を速やかに明らかにする必要がある。本研究では、金ナノ粒子の特性を活用したプローブ設計を通して、アフィニティラベリングの新規技術を開発した。本成果により、特に同定が困難であった低親和性糖鎖や希少な天然生物活性化合物において標的タンパク質とのラベリング反応の効率化や濃縮精製工程の簡便化が可能となり、標的同定の加速化および一般化に貢献した。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (31 results)

All 2021 2020 2019 2018 Other

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 1 results) Presentation (22 results) (of which Int'l Joint Research: 9 results,  Invited: 7 results) Remarks (2 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Clickable gold-nanoparticles as generic probe precursors for facile photoaffinity labeling application2021

    • Author(s)
      Mori Kanna、Sakurai Kaori
    • Journal Title

      Organic & Biomolecular Chemistry

      Volume: 19 Issue: 6 Pages: 1268-1273

    • DOI

      10.1039/d0ob01688h

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Phospholipid-Dependent Functions of a Macrocyclic Analogue of the Ion-Channel-Forming Antibiotic Gramicidin A2020

    • Author(s)
      Ji Mao, Hiroaki Itoh, Kaori Sakurai, Masayuki Inoue
    • Journal Title

      Chemical and Pharmaceutical Bulletin

      Volume: 68 Issue: 2 Pages: 173-178

    • DOI

      10.1248/cpb.c19-00967

    • NAID

      130007793433

    • ISSN
      0009-2363, 1347-5223
    • Year and Date
      2020-02-01
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Interactions of OSW-1 with Lipid Bilayers in Comparison with Digitonin and Soyasaponin.2020

    • Author(s)
      Raymond Malabed, Shinya Hanashima, Michio Murata, Kaori Sakurai
    • Journal Title

      Langmuir

      Volume: 36 Issue: 13 Pages: 3600-3610

    • DOI

      10.1021/acs.langmuir.9b03957

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Computational and Experimental Analysis on the Conformational Preferences of Anticancer Saponin OSW-12019

    • Author(s)
      Fukaya Keisuke、Urabe Daisuke、Hiraizumi Masato、Noguchi Keiichi、Matsumoto Takashi、Sakurai Kaori
    • Journal Title

      The Journal of Organic Chemistry

      Volume: 85 Issue: 2 Pages: 339-344

    • DOI

      10.1021/acs.joc.9b02085

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clickable gold nanoparticles for streamlining capture, enrichment and release of alkyne-labelled proteins2019

    • Author(s)
      Narita Sho、Kobayashi Naohiro、Mori Kanna、Sakurai Kaori
    • Journal Title

      Bioorganic & Medicinal Chemistry Letters

      Volume: 29 Issue: 24 Pages: 126768-126768

    • DOI

      10.1016/j.bmcl.2019.126768

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Development of Chemical Probes for Functional Analysis of Anticancer Saponin OSW‐12019

    • Author(s)
      Komatsu Rina、Sakurai Kaori
    • Journal Title

      The Chemical Record

      Volume: 19 Issue: 12 Pages: 2362-2369

    • DOI

      10.1002/tcr.201900042

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] Comparative study of multivalent electrophiles for affinity labeling of carbohydrate binding proteins.2021

    • Author(s)
      Shione Kamoshita, Saho Matsui, Nanako Suto, Kaori Sakurai.
    • Organizer
      JSPS A3 Foresight Program, Asian Chemical Probe Research Hub, A3 Young Scientists’ Meeting
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Evaluation of gold nanoparticle-based affinity labeling probes bearing electrophilic groups.2021

    • Author(s)
      Shione Kamoshita, Saho Matsui, Nanako Suto, Kaori Sakurai.
    • Organizer
      日本化学会第101 回春季年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Functional analysis of azide-functionalized gold nanoparticles toward affinity labeling.2021

    • Author(s)
      Atsushi Adachi, Nanako Suto, Kaori Sakurai.
    • Organizer
      日本化学会第101 回春季年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Multivalent affinity labeling probes for target protein analysis2020

    • Author(s)
      K. Sakurai
    • Organizer
      Departmental seminar (online), Hunter College, City University of New York.
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Development of gold nanoparticle-based clickable photoaffinity labeling agent for target protein identification2019

    • Author(s)
      Kanna Mori, Naohiro Kobayashi, Kaori Sakurai
    • Organizer
      日本ケミカルバイオロジー学会第14回年会
    • Related Report
      2019 Research-status Report
  • [Presentation] Development of gold nanoparticle-based affinity labeling probes for target protein analysis2019

    • Author(s)
      Nanako Suto Takumi Umezawa, Kaori Sakurai,
    • Organizer
      日本ケミカルバイオロジー学会第14回年会
    • Related Report
      2019 Research-status Report
  • [Presentation] Development of gold-nanoparticle based probes for target identification and analysis of bioactive small molecules2019

    • Author(s)
      Kaori Sakurai,
    • Organizer
      Asian Chemical Biology Initiative Yangon Meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Development of gold nanoparticle-based multivalent photoaffinity probes toward exploration of carbohydrate-protein interaction2019

    • Author(s)
      Kaori Sakurai
    • Organizer
      2nd Australasian Glycoscience Symposium, HUPO2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Development of gold nanoparticle-based affinity labeling probes for analyzing carbohydrate-binding proteins2019

    • Author(s)
      Nanako Suto, Kaori Sakurai
    • Organizer
      2nd Australasian Glycoscience Symposium, HUPO2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Development of gold nanoparticle-based clickable photoaffinity probes for target protein identification2019

    • Author(s)
      Kanna Mori, Kaori Sakurai
    • Organizer
      2nd Australasian Glycoscience Symposium, HUPO2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Development of Gold Nanoparticle-Based Click- Photocapture Agents for Target Protein Identification2019

    • Author(s)
      Kanna Mori, Naohiro Kobayashi, Kaori Sakurai
    • Organizer
      日本化学会第99回春季年会
    • Related Report
      2019 Research-status Report
  • [Presentation] Development of Gold Nanoparticle-Based Affinity Labeling Probes for Target Protein Analysis2019

    • Author(s)
      Nanako Suto Takumi Umezawa, Kaori Sakurai,
    • Organizer
      日本化学会第99回春季年会
    • Related Report
      2019 Research-status Report
  • [Presentation] 糖鎖結合タンパク質探索のための金ナノ粒子プローブ開発2019

    • Author(s)
      須藤菜々子、櫻井香里
    • Organizer
      Nanotech CUPAL AIST TIA ナノバイオサマースクール
    • Related Report
      2019 Research-status Report
  • [Presentation] 金ナノ粒子アフィニティーラベリングプローブの開発2019

    • Author(s)
      鴨下潮音、櫻井香里
    • Organizer
      Nanotech CUPAL AIST TIA ナノバイオサマースクール
    • Related Report
      2019 Research-status Report
  • [Presentation] Target identification: Chemical Approaches2019

    • Author(s)
      Kaori Sakurai
    • Organizer
      Asian Chemical Biology Initiative Jakarta Meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Development of gold-nanoparticle based probes for target identification and analysis of bioactive small molecules2019

    • Author(s)
      Kaori Sakurai,
    • Organizer
      Asian Chemical Biology Initiative Yangon Meeting, Yangon, Myanmar
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Development of gold nanoparticle-based affinity labeling probes for target protein analysis2019

    • Author(s)
      Nanako Suto, Takumi Umezawa, Kaori Sakurai
    • Organizer
      日本化学会第 99 春季年会
    • Related Report
      2018 Research-status Report
  • [Presentation] Development of gold nanoparticle-based click-photocapture agents for target protein identification2019

    • Author(s)
      Kanna Mori, Naohiro Kobayashi, Kaori Sakurai
    • Organizer
      日本化学会第 99 春季年会
    • Related Report
      2018 Research-status Report
  • [Presentation] Development of Gold-Nanoparticle Based Probes for Target Identification and Analysis of Bioactive Small Molecules2018

    • Author(s)
      Kaori Sakurai,
    • Organizer
      A3 Foresight Program Round Table Meeting on Chemical Probe Research Hub
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Development of gold-nanoparticle based probes for target identification and analysis of bioactive small molecules2018

    • Author(s)
      Kaori Sakurai,
    • Organizer
      Singapore Chemistry Conference 2018 (SICC-10)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 抗癌活性サポニンOSW-1の化学プローブを用いたOSBPパラログ選択的結合活性の解析2018

    • Author(s)
      小松莉奈、磯貝菜穂、櫻井香里
    • Organizer
      GlycoTokyo 2018
    • Related Report
      2018 Research-status Report
  • [Presentation] Chemical-probe based approach to binding interaction analysis of anticancer natural product OSW-12018

    • Author(s)
      Rina Komatsu, Naho Isogai, Kaori Sakurai
    • Organizer
      A3 Foresight Program Young researchers Meeting on Chemical Probe Research Hub
    • Related Report
      2018 Research-status Report
  • [Remarks] 標的タンパク質探索への新しいアプローチの開発

    • Related Report
      2020 Annual Research Report
  • [Remarks] Easily assembled gold nanoparticle scaffolding

    • URL

      https://www.eurekalert.org/pub_releases/2021-02/tuoa-eag020121.php

    • Related Report
      2020 Annual Research Report
  • [Patent(Industrial Property Rights)] 化合物、該化合物を用いた金属ナノ粒子複合体、及び標的分子の検出法2020

    • Inventor(s)
      櫻井香里
    • Industrial Property Rights Holder
      櫻井香里
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Related Report
      2020 Annual Research Report

URL: 

Published: 2018-04-23   Modified: 2022-01-27  

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