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Advance of enzymomics study for establishment of disease diagnosis platform

Research Project

Project/Area Number 23K23484
Project/Area Number (Other) 22H02217 (2022-2023)
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeMulti-year Fund (2024)
Single-year Grants (2022-2023)
Section一般
Review Section Basic Section 37030:Chemical biology-related
Research InstitutionThe University of Tokyo

Principal Investigator

Komatsu Toru  東京大学, 大学院薬学系研究科(薬学部), 准教授 (40599172)

Co-Investigator(Kenkyū-buntansha) 水野 忠快  東京大学, 大学院薬学系研究科(薬学部), 助教 (90736050)
Project Period (FY) 2024-04-01 – 2025-03-31
Project Status Completed (Fiscal Year 2024)
Budget Amount *help
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2024: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2023: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2022: ¥11,180,000 (Direct Cost: ¥8,600,000、Indirect Cost: ¥2,580,000)
Keywordsケミカルバイオロジー / 創薬化学
Outline of Research at the Start

自動合成を用いたプローブ合成,規格化された計測条件の設定,バイアスをかけずに1分子計測データを解析することができる解析系の構築,をもって,安定してデータを蓄積していくことが可能な仕組みが整ってきた.これを用いて,特に健常者の血液検体を中心として1分子酵素活性データの蓄積をおこない,アトラスの作成を進める.これを参照データとして用いることにより,特定の疾患に由来する生体サンプルが与えられた際に,この参照データからの変化によって疾患に関わるバイオマーカーの迅速な探索をおこなっていくことが可能になると期待される.

Outline of Final Research Achievements

We have established the enzymomics platform based on single-moelcule enzyme activity assay by establishment of (1) automated probe synthesis platform, (2) standardized assay platform, and (3) non-biased data analysis method. During the research period, 6 patents were applied, and the individual results of biomaker discovery was reported in jounals such as J. Am. Chem. Soc., Chem. Sci., Adv. Sci., and Cell Rep. Methods.

Academic Significance and Societal Importance of the Research Achievements

これまで 10^6-10^9 分子を集団として扱うことが通常であったタンパク質機能解析において,1分子レベルの網羅的解析をおこなうという概念を導入し,その実用性を示すことに成功したことで,新たなタンパク質機能解析の方法論の提案に繋がった(総説投稿中).また,研究成果の実用化については,研究期間中に出願された特許6件のうち5件について,研究機関である東京大学と膵臓がんをはじめとする疾患の早期診断技術の開発を目指す大学発スタートアップ企業の間にライセンス契約が締結され,成果の社会実装に向けた先鞭がつけられた.

Report

(4 results)
  • 2024 Annual Research Report   Final Research Report ( PDF )
  • 2023 Annual Research Report
  • 2022 Annual Research Report
  • Research Products

    (36 results)

All 2025 2024 2023 2022

All Journal Article (15 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 15 results,  Open Access: 9 results) Presentation (15 results) (of which Int'l Joint Research: 4 results,  Invited: 13 results) Book (2 results) Patent(Industrial Property Rights) (4 results) (of which Overseas: 1 results)

  • [Journal Article] Identification of a pancreatic juice-specific fluorescent probe through 411 probes activated by aminopeptidases/proteases or phosphatases/phosphodiesterases2025

    • Author(s)
      Seki Yusuke、Ishizawa Takeaki、Watanabe Genki、Komatsu Toru、Nanjo Aika、Ueno Tasuku、Urano Yasuteru、Kawaguchi Mitsuyasu、Nakagawa Hidehiko、Hasegawa Kiyoshi
    • Journal Title

      HPB

      Volume: 27 Issue: 2 Pages: 150-158

    • DOI

      10.1016/j.hpb.2024.10.012

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Single-Molecule Oxidoreductase Activity Analysis for Activity-Based Diagnosis Based on Proteoform Alterations2025

    • Author(s)
      Mayano Minoda、Junpei Hatakeyama、Norimichi Nagano、Tadahaya Mizuno、Takumi Iwasaka、Sho Shiga、Kazuki Takahashi、Hideto Hiraide、Shingo Sakamoto、Yu Kagami、Ayumi Kashiro、Kazufumi Honda、Yuki Sugiura、Kazuhiko Mishima、Masayo Kaneko Mishima、Hiroyuki Kusuhara、Yasuteru Urano、Toru Komatsu
    • Journal Title

      Journal of the American Chemical Society

      Volume: 147(6) Issue: 6 Pages: 4743-4751

    • DOI

      10.1021/jacs.4c07624

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Application of Intramolecular O-to-N Phosphoryl Transfer Reaction to Design Fluorogenic Probes to Detect Activities of Enzymes That Metabolize Short Peptides and Acylamino Acids2025

    • Author(s)
      Risako Sawayama、Mayano Minoda、Hirotatsu Kojima、Takayoshi Okabe、Yukari Isayama、Kazuki Kato、Hiroshi Nishimasu、Yasuteru Urano、Toru Komatsu
    • Journal Title

      ACS Sensors

      Volume: 10(2) Issue: 2 Pages: 664-670

    • DOI

      10.1021/acssensors.4c03402

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of near-infrared fluorescent probe for the selective detection of severe hypoxia2025

    • Author(s)
      Takafumi Kasai, Kyohhei Fujita, Toru Komatsu, Tasuku Ueno, Ryosuke Kojima, Kenjiro Hanaoka, Yasuteru Urano
    • Journal Title

      RCS Chemical Biology

      Volume: 6 Issue: 3 Pages: 449-456

    • DOI

      10.1039/d4cb00243a

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] γ-Secretase cleaves bifunctional fatty acid-conjugated small molecules with amide bonds in mammalian cells2024

    • Author(s)
      Kai Tahara, Akinobu Nakamura, Xiaotong Wang, Keishi Mitamura, Yuki Ichihashi, Keiko Kano, Emi Mishiro-Sato, Kazuhiro Aoki, Yasuteru Urano, Toru Komatsu, Shinya Tsukiji
    • Journal Title

      ACS Chemical Biology

      Volume: 19 Issue: 12 Pages: 2438-2450

    • DOI

      10.1021/acschembio.4c00432

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A general fluorescence off/on strategy for fluorogenic probes: Steric repulsion-induced twisted intramolecular charge transfer (sr-TICT)2024

    • Author(s)
      Hanaoka Kenjiro、Ikeno Takayuki、Iwaki Shimpei、Deguchi Sayaka、Takayama Kazuo、Mizuguchi Hiroyuki、Tao Fumiya、Kojima Nobuhiko、Ohno Hisashi、Sasaki Eita、Komatsu Toru、Ueno Tasuku、Maeda Kazuya、Kusuhara Hiroyuki、Urano Yasuteru
    • Journal Title

      Science Advances

      Volume: 10 Issue: 7

    • DOI

      10.1126/sciadv.adi8847

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of activity-based biomarkers for early-stage pancreatic tumors in blood using single-molecule enzyme activity screening2024

    • Author(s)
      Shingo Sakamoto、Hideto Hiraide、Mayano Minoda、Nozomi Iwakura、Misa Suzuki、Jun Ando、Chiharu Takahashi、Ikuko Takahashi、Kazue Murai、Yu Kagami、Tadahaya Mizuno、Tohru Koike、Satoshi Nara、Chigusa Morizane、Susumu Hijioka、Ayumi Kashiro、Kazufumi Honda、Rikiya Watanabe、Yasuteru Urano、Toru Komatsu
    • Journal Title

      Cell Reports Methods

      Volume: 4 Issue: 1 Pages: 100688-100688

    • DOI

      10.1016/j.crmeth.2023.100688

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Modular Design Platform for Activatable Fluorescence Probes Targeting Carboxypeptidases Based on ProTide Chemistry2023

    • Author(s)
      Kuriki Yugo、Sogawa Mari、Komatsu Toru、Kawatani Minoru、Fujioka Hiroyoshi、Fujita Kyohhei、Ueno Tasuku、Hanaoka Kenjiro、Kojima Ryosuke、Hino Rumi、Ueo Hiroki、Ueo Hiroaki、Kamiya Mako、Urano Yasuteru
    • Journal Title

      Journal of the American Chemical Society

      Volume: 146 Issue: 1 Pages: 521-531

    • DOI

      10.1021/jacs.3c10086

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Thioester‐Based Coupled Fluorogenic Assays in Microdevice for the Detection of Single‐Molecule Enzyme Activities of Esterases with Specified Substrate Recognition2023

    • Author(s)
      Ukegawa Tatsuya、Komatsu Toru、Minoda Mayano、Matsumoto Takuya、Iwasaka Takumi、Mizuno Tadahaya、Tachibana Ryo、Sakamoto Shingo、Hanaoka Kenjiro、Kusuhara Hiroyuki、Honda Kazufumi、Watanabe Rikiya、Urano Yasuteru
    • Journal Title

      Advanced Science

      Volume: 11 Issue: 10 Pages: 2306559-2306559

    • DOI

      10.1002/advs.202306559

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of fluorogenic substrates for colorectal tumor-related neuropeptidases for activity-based diagnosis2023

    • Author(s)
      Norimichi Nagano、Yuki Ichihashi、Toru Komatsu、Hiroyuki Matsuzaki、Keisuke Hata、Toshiaki Watanabe、Yoshihiro Misawa、Misa Suzuki、Shingo Sakamoto、Yu Kagami、Ayumi Kashiro、Keiko Takeuchi、Yukihide Kanemitsu、Hiroki Ochiai、Rikiya Watanabe、Kazufumi Honda、Yasuteru Urano
    • Journal Title

      Chemical Science

      Volume: 14 Issue: 17 Pages: 4495-4499

    • DOI

      10.1039/d2sc07029d

    • Related Report
      2023 Annual Research Report 2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of pathway-oriented screening to identify compounds to control 2-methylglyoxal metabolism in tumor cells2023

    • Author(s)
      Yanagi Kouichi、Komatsu Toru、Fujikawa Yuuta、Kojima Hirotatsu、Okabe Takayoshi、Nagano Tetsuo、Ueno Tasuku、Hanaoka Kenjiro、Urano Yasuteru
    • Journal Title

      Communications Chemistry

      Volume: 6 Issue: 1 Pages: 68-68

    • DOI

      10.1038/s42004-023-00864-y

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of a fluorescent probe library enabling efficient screening of tumour-imaging probes based on discovery of biomarker enzymatic activities2022

    • Author(s)
      Kuriki Yugo、Yoshioka Takafusa、Kamiya Mako、Komatsu Toru、Takamaru Hiroyuki、Fujita Kyohhei、Iwaki Hirohisa、Nanjo Aika、Akagi Yuki、Takeshita Kohei、Hino Haruaki、Hino Rumi、Kojima Ryosuke、Ueno Tasuku、Hanaoka Kenjiro、Abe Seiichiro、Saito Yutaka、Nakajima Jun、Urano Yasuteru
    • Journal Title

      Chemical Science

      Volume: 13 Issue: 16 Pages: 4474-4481

    • DOI

      10.1039/d1sc06889j

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Molecular design of near-infrared (NIR) fluorescent probes targeting exopeptidase and application for detection of dipeptidyl peptidase 4 (DPP-4) activity2022

    • Author(s)
      Hoshino Yuki、Hanaoka Kenjiro、Sakamoto Kei、Yasunaga Masahiro、Kojima Takashi、Kotani Daisuke、Nomoto Ayumu、Sasaki Eita、Komatsu Toru、Ueno Tasuku、Takamaru Hiroyuki、Saito Yutaka、Seto Yasuyuki、Urano Yasuteru
    • Journal Title

      RSC Chemical Biology

      Volume: - Issue: 7 Pages: 859-867

    • DOI

      10.1039/d1cb00253h

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] General Design Strategy to Precisely Control the Emission of Fluorophores via a Twisted Intramolecular Charge Transfer (TICT) Process2022

    • Author(s)
      Hanaoka Kenjiro、Iwaki Shimpei、Yagi Kiyoshi、Myochin Takuya、Ikeno Takayuki、Ohno Hisashi、Sasaki Eita、Komatsu Toru、Ueno Tasuku、Uchigashima Motokazu、Mikuni Takayasu、Tainaka Kazuki、Tahara Shinya、Takeuchi Satoshi、Tahara Tahei、Uchiyama Masanobu、Nagano Tetsuo、Urano Yasuteru
    • Journal Title

      Journal of the American Chemical Society

      Volume: 144 Issue: 43 Pages: 19778-19790

    • DOI

      10.1021/jacs.2c06397

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Rapid imaging of lung cancer using a red fluorescent probe to detect dipeptidyl peptidase 4 and puromycin-sensitive aminopeptidase activities2022

    • Author(s)
      Kawashima Shun、Yoshida Daisuke、Yoshioka Takafusa、Ogasawara Akira、Fujita Kyohhei、Yanagiya Masahiro、Nagano Masaaki、Konoeda Chihiro、Hino Haruaki、Kitano Kentaro、Sato Masaaki、Hino Rumi、Kojima Ryosuke、Komatsu Toru、Kamiya Mako、Urano Yasuteru、Nakajima Jun
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 12665-9

    • DOI

      10.1038/s41598-022-12665-9

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 1分子レベルの酵素活性解析に基づく疾患診断技術の開発2025

    • Author(s)
      小松徹
    • Organizer
      APPW 2025(第130回日本解剖学会/第102回日本生理学会/第98回日本薬理学会合同大会)
    • Related Report
      2024 Annual Research Report
    • Invited
  • [Presentation] 酵素(生体触媒)のはたらきを1分子レベルで見る~1分子計測 × ケミカルプローブ全自動合成に基づく疾患診断技術の開発~2024

    • Author(s)
      小松徹
    • Organizer
      第6回産総研化学研究シンポジウム
    • Related Report
      2024 Annual Research Report
    • Invited
  • [Presentation] 酵素のはたらきを1分子レベルで見る~1分子計測 × ケミカルプローブ全自動合成に基づく疾患診断技術の開発~2024

    • Author(s)
      小松徹
    • Organizer
      第16回光塾
    • Related Report
      2024 Annual Research Report
    • Invited
  • [Presentation] 1分子レベルの酵素活性検出に基づく疾患診断技術の開発2024

    • Author(s)
      小松徹
    • Organizer
      第12回大隅ライフサイエンス研究会
    • Related Report
      2024 Annual Research Report
    • Invited
  • [Presentation] Identification of activity-based biomarkers for early-stage pancreatic tumors in blood using single-molecule enzyme activity screening2024

    • Author(s)
      Toru Komatsu
    • Organizer
      The 3rd International Symposium on Biofunctional Chemistry
    • Related Report
      2024 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Development of single-molecule enzyme activity profiling platform for activity-based diagnosis of early stage pancreatic tumor2023

    • Author(s)
      Toru Komatsu
    • Organizer
      国際交流シンポジウム 次世代薬学 アジアシンポジウム(日本薬学会 第 144 年会)
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 有機小分子蛍光プローブと1分子計測技術の融合による血液中1分子酵素活性網羅的解析技術の開発2023

    • Author(s)
      小松徹
    • Organizer
      日本薬学会 第 144 年会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 1分子レベルの酵素活性網羅的解析に基づく疾患診断技術基盤の開発と応用2023

    • Author(s)
      小松徹
    • Organizer
      バイオインタラクション(BIRA)研究会 第 23 回ワークショップ
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 1分子レベルのタンパク質機能検出による疾患診断技術の開発2023

    • Author(s)
      小松徹, 渡邉力也, 水野忠快, 本田一文, 坂本眞伍
    • Organizer
      第 40 回メディシナルケミストリーシンポジウム
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Proteoform レベルの酵素活性網羅的解析に基づく疾患診断技術の開発2023

    • Author(s)
      小松徹
    • Organizer
      第 1 回 ATF コンファレンス 2023年11月13日
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Proteoform レベルの酵素活性網羅的解析に基づく疾患診断技術の開発2023

    • Author(s)
      小松徹
    • Organizer
      レドックス R&D 戦略委員会 第 2 回 夏のシンポジウム
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 1分子レベルの酵素活性網羅的解析に基づく疾患診断技術の開発2022

    • Author(s)
      小松徹
    • Organizer
      千里ライフサイエンス振興財団 新適塾「未来創薬への誘い」第57回講演会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 1分子レベルの酵素活性網羅的解析に基づく 疾患診断技術の開発2022

    • Author(s)
      小松徹
    • Organizer
      第 16 回メタボロームシンポジウム
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Development of single-molecule enzyme activity-based protein profiling (SEAP) strategy for the detection of disease-related enzyme activities in blood samples2022

    • Author(s)
      Toru Komatsu, Shingo Sakamoto, Tadahaya Mizuno, Kazufumi Honda, Rikiya Watanabe, Yasuteru Urano
    • Organizer
      Redox Week 2022
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Development of single-molecule enzyme activity-based protein profiling (SEAP) strategy for the detection of disease-related enzyme activities in blood samples2022

    • Author(s)
      Toru Komatsu, Shingo Sakamoto, Yu Kagami, Tadahaya Mizuno, Kazufumi Honda, Rikiya Watanabe, Yasuteru Urano
    • Organizer
      International Chemical Biology Society Meeting 2022
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Book] 疾患と関わる酵素の働きを夾雑環境下で「視る」2023

    • Author(s)
      小松徹
    • Total Pages
      208
    • Publisher
      化学同人
    • ISBN
      9784759814057
    • Related Report
      2022 Annual Research Report
  • [Book] 茶カテキンによるエピジェネティック制御因子への関与2022

    • Author(s)
      小松徹,小倉大輝,浦野泰照
    • Total Pages
      333
    • Publisher
      シーエムシー出版
    • ISBN
      9784781316871
    • Related Report
      2022 Annual Research Report
  • [Patent(Industrial Property Rights)] 化合物の合成方法2024

    • Inventor(s)
      小松徹,浦野泰照,箕田麻弥乃
    • Industrial Property Rights Holder
      小松徹,浦野泰照,箕田麻弥乃
    • Industrial Property Rights Type
      特許
    • Filing Date
      2024
    • Related Report
      2024 Annual Research Report
  • [Patent(Industrial Property Rights)] ペプチド含有化合物の製造方法2024

    • Inventor(s)
      小松徹,浦野泰照
    • Industrial Property Rights Holder
      小松徹,浦野泰照
    • Industrial Property Rights Type
      特許
    • Filing Date
      2024
    • Related Report
      2024 Annual Research Report
  • [Patent(Industrial Property Rights)] 固相抽出を利用した蛍光プローブライブラリの調製方法、及びこれを用いた酵素活性計測方法2022

    • Inventor(s)
      浦野泰照,小松徹,鏡味優,坂本眞伍,渡邉力也
    • Industrial Property Rights Holder
      浦野泰照,小松徹,鏡味優,坂本眞伍,渡邉力也
    • Industrial Property Rights Type
      特許
    • Filing Date
      2022
    • Related Report
      2022 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 3.浦野泰照,小松徹,鏡味優,坂本眞伍,笠井貴文,渡邉力也2022

    • Inventor(s)
      浦野泰照,小松徹,鏡味優,坂本眞伍,笠井貴文,渡邉力也
    • Industrial Property Rights Holder
      浦野泰照,小松徹,鏡味優,坂本眞伍,笠井貴文,渡邉力也
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2022-079082
    • Filing Date
      2022
    • Related Report
      2022 Annual Research Report

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Published: 2022-04-19   Modified: 2026-01-16  

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