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Development of cancer cell-specific fluorescent probes targeting angiogenic factors

Research Project

Project/Area Number 21K05315
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 37030:Chemical biology-related
Research InstitutionShibaura Institute of Technology

Principal Investigator

Hatano Akihiko  芝浦工業大学, 工学部, 教授 (10333163)

Co-Investigator(Kenkyū-buntansha) 福井 浩二  芝浦工業大学, システム理工学部, 教授 (80399807)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords血管新生 / チミジンホスホリラーゼ / 診断薬 / 蛍光色素 / 早期発見 / 非天然ヌクレオシド / 血管新生因子 / 核酸代謝酵素 / 蛍光 / ベンゾイミダゾール / ヌクレオシド / ピリミジンヌクレオシドホスホリラーゼ / パイ平面拡張イミダゾール / プローブ分子 / 蛍光応答 / 園頭反応 / 蛍光イメージング / 蛍光共鳴エネルギー移動 / 分子プローブ
Outline of Research at the Start

本研究は,癌などの血管新生病を早期発見するために,リアルタイムイメージング薬を開発することを目的とする。すなわち,血管新生因子として知られているチミジンホスホリラーゼ(TP)の酵素活性を利用して,患部を蛍光染色する診断薬の開発を行う。

Outline of Final Research Achievements

In this study, we developed a diagnostic agent that marks cancer tissue with fluorescence. When cancer cells proliferate, they create new small blood vessels to draw in nutrients from nearby blood vessels. This phenomenon is called angiogenesis, and it occurs during the process of tumor growth. Thymidine phosphorylase is known to be involved in this angiogenesis factor. We developed a diagnostic agent that emits fluorescence when it undergoes a phospholysis catalyzed by thymidine phosphorylase. We succeeded in synthesizing three fluorescent base analogues that were substrates for thymidine phosphorylase.

Academic Significance and Societal Importance of the Research Achievements

現在,癌の治療は手術療法,化学療法,放射線治療があるが,早期に発見して手術にて切除を行うことが肝心である。しかし,1)癌細胞と正常細胞の境界が分かりにくい(広範囲に切除する必要がある),2)病理検査を行なって術域や術式を決める必要があり,時間を要する(患者負荷が増加)。
癌細胞は無限増殖能を獲得しているため,正常細胞より栄養を欲するため,新しく血管を作る血管新生が行われる。申請者は,血管新生を活発に行っている部位をマーキングする診断薬の開発を行った。血管新生因子であるチミジンホスホリラーゼの活性に応じて蛍光が変化する化合物のデザインと合成を行った。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (18 results)

All 2023 2022 2021

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Open Access: 2 results) Presentation (14 results) (of which Int'l Joint Research: 11 results)

  • [Journal Article] Introduction of pseudo-base benzimidazole derivatives into nucleosides via base exchange by a nucleoside metabolic enzyme2023

    • Author(s)
      1)A. Hatano, R. Matsuzaka, G. Shimane, H. Wakana, K. Suzuki, C. Nishioka, A. Kojima, M. Kidowaki
    • Journal Title

      Bioorganic & Medicinal Chemistry

      Volume: 91 Pages: 117411-117411

    • DOI

      10.1016/j.bmc.2023.117411

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Supramolecular Conjugation between 18-Crown 6-Ether and Tannic Acid with Unique pH Responsiveness2023

    • Author(s)
      Endo Saki、Sarai Mahiro、Hatano Akihiko、Niikura Kenichi
    • Journal Title

      Chemistry Letters

      Volume: 52 Issue: 6 Pages: 455-458

    • DOI

      10.1246/cl.230093

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Reagentless Sensing of Vancomycin Using an Indium Tin Oxide Electrode Grafted with Molecularly Imprinted Polymer including Ferrocenyl Group2021

    • Author(s)
      Eguchi, Haruto; Hatano, Akihiko; Yoshimi, Yasuo
    • Journal Title

      Sensors

      Volume: 24 Issue: 24 Pages: 8338-8338

    • DOI

      10.3390/s21248338

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] A disposable vancomycin sensor using molecularly imprinted carbon paste on a paper chip2021

    • Author(s)
      Aaryashree; Ebisawa, Haruki; Azuma, Sayaka; Hatano, Akihiko; Yoshimi, Yasuo
    • Journal Title

      Chemical Sensors

      Volume: 38 Pages: 76-78

    • NAID

      40022727851

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Synthesis of pentostatin precursor with pyrimidine nucleoside phosphorylase2023

    • Author(s)
      Rai Hamano, Akihiko Hatano, Riki Matsuzaka
    • Organizer
      3rd Japan-Switzerland-Germany Workshop on Biocatalysis and Bioprocess Development
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Chemoenzymatic synthesis of unnatural nucleoside with stable isotopes2023

    • Author(s)
      Genki SHIMANE, Nanae Terado, Akihiko HATANO
    • Organizer
      rd Japan-Switzerland-Germany Workshop on Biocatalysis and Bioprocess Development
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ynthesis of spin-labeled RNAs to elucidate the function of reverse transcriptase2023

    • Author(s)
      Genki SHIMANE, Akihiko HATANO, Nanae TERADO
    • Organizer
      SEATUC 2023
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Development of the one-dimensional integrated inhibitor of deoxynojirimycin using DNA sequences2023

    • Author(s)
      Ryu MAYUMI, Akihiko HATANO
    • Organizer
      SEATUC 2023
    • Related Report
      2023 Annual Research Report 2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Introduction of Benzimidazole as Purine Analog into Nucleoside Structure by Base-Exchange Reaction of Nucleoside Metabolism Enzyme2023

    • Author(s)
      Riki MATSUSAKA, Akihiko HATANO
    • Organizer
      SEATUC 2023
    • Related Report
      2023 Annual Research Report 2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Examination of chemical enzyme synthesis method to introduce multiple stable isotopes into nucleoside molecular structure2023

    • Author(s)
      Genki SHIMANE, Akihiko HATANO, Nanae TERADO
    • Organizer
      SEATUC 2023
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Synthesis of spin-labeled RNAs to elucidate the function of reverse transcriptase2023

    • Author(s)
      Nagihiro Miyahara, Nanae Terado, Saki Kaneko, Akihiko Hatano
    • Organizer
      SEATUC 2023
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Effects of Functional Groups Recognition of Nucleoside Structure for Phosphorolysis with Pyrimidine Nucleoside Phosphorylase PyNP2023

    • Author(s)
      Rei HAMANO, Koichi OTSUKIi, Akihiko HATANO
    • Organizer
      SEATUC 2023
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Examination of chemical enzyme synthesis method to introduce multiple stable isotopes into uridine molecular structure2022

    • Author(s)
      Genki SHIMANE, Akihiko HATANO
    • Organizer
      Active Enzyme Molecules, 2022, in Toyama
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Base Exchange Effects of Benzimidazole as Pseudo Purine Base into Nucleoside Structure with Nucleoside Metabolic Enzyme2022

    • Author(s)
      Riki MATSUSAKA, Takumi HAYASHIDA, Akihiko HATANO
    • Organizer
      Active Enzyme Molecules, 2022, in Toyama
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Effects of Functional Groups Recognition of Nucleoside substrate for Phosphorolysis with Nucleoside Metabolic Enzyme PyNP2022

    • Author(s)
      Ryu MAYUMI, Koichi OTSUKI, Akihiko HATANO
    • Organizer
      Active Enzyme Molecules, 2022, in Toyama
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] ピリミジンヌクレオシドホスホリラーゼPyNP によるリボース部位修飾 ヌクレオシドの反応性2022

    • Author(s)
      間弓 利勇・大槻 晃一・幡野明彦
    • Organizer
      本化学会第102春季年会(2022)
    • Related Report
      2021 Research-status Report
  • [Presentation] 核酸代謝酵素PyNPによるヌクレオシドへのプリン類似体ベンゾイミダゾール化合物の導入2022

    • Author(s)
      松坂理希・幡野明彦
    • Organizer
      本化学会第102春季年会(2022)
    • Related Report
      2021 Research-status Report
  • [Presentation] レーザーマイクロダイセクション装置によるがん細胞特異的に見られる核内封入体構成成分の同定2022

    • Author(s)
      水口 海,八谷 如美,幡野 明彦
    • Organizer
      本化学会第102春季年会(2022)
    • Related Report
      2021 Research-status Report

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Published: 2021-04-28   Modified: 2025-01-30  

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