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Fluorescent super-resolution imaging probe using novel chemical switching mechanism

Research Project

Project/Area Number 19K22255
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 37:Biomolecular chemistry and related fields
Research InstitutionOsaka University

Principal Investigator

Kikuchi Kazuya  大阪大学, 工学研究科, 教授 (70292951)

Project Period (FY) 2019-06-28 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2020: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2019: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Keywords光スイッチング / 蛍光プローブ / 光異性化 / 超解像イメージング / 蛋白質可逆ラベル化 / 化学プローブ / RESOLFT / 蛋白質ラベル化
Outline of Research at the Start

本研究では、新たな蛋白質・合成蛍光プローブのペアを用い、化学原理に基づき蛍光スイッチ機能を持つ超解像イメージングプローブを設計・開発する。分子が発する蛍光を制御することは、新時代の生体イメージングの鍵となる。生体シグナルに応じて、標的分子が現れ消えていく様子を見るには、その標的分子を蛍光色素で特異的に標識し、その色素の蛍光特性を変化させるスイッチ機能が必要である。これらの課題を解決することを目的とし、化学からのアプローチにより、超解像イメージングに応用可能な新しいスイッチ機能を持つプローブの開発を行う。

Outline of Final Research Achievements

In this study, we developed photoswitching fluorescent probes by light irradiation. We synthesized and evaluated a series of photoswitching probes comprised of a fluorophore, a quenching group, and an arylazopyrazole (AAP) as a structural controller. AAP has excellent photochromic property and triggers fluorophore/quencher contact quenching and its recovery upon photoirradiation. The control of fluorescence quenching enabled switching of fluorescence intensity of about 60% for SC1 and about 40% for SC2 and SC3. Furthermore, we demonstrated reversible photoswitching without any additive and resistance to photobleaching and photofatigue after repeated cycles of photoirradiation.

Academic Significance and Societal Importance of the Research Achievements

蛍光スイッチング分子は、光照射により蛍光強度を制御できる性質を持ち、超解像顕微鏡法で、光の回折分解能を越えて生体分子の局在を可視化するために用いられる。これらの分子を用いた超解像顕微鏡による生物学研究への応用においては添加剤の使用や光安定性の欠如など未だ課題があったが、今回開発した分子スイッチングのメカニズムを利用することで、添加剤フリーで蛍光強度が繰り返し変化することが明らかとなり、今後の超解像イメージングに応用することで、長時間の微細構造の観察による生命科学研究の進展が期待される。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (29 results)

All 2022 2021 2020 2019

All Journal Article (19 results) (of which Int'l Joint Research: 9 results,  Peer Reviewed: 19 results,  Open Access: 10 results) Presentation (7 results) (of which Int'l Joint Research: 6 results,  Invited: 7 results) Book (2 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] カテプシン K 活性の検出を目指した Off-On スイッチング 19F MRI ナノプローブの開発2022

    • Author(s)
      小西祐輝、杉原文徳、蓑島維文、菊地和也
    • Journal Title

      日本分子イメージング学会機関誌(JSMI Report)

      Volume: 15 Pages: 29-33

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cardioluminescence in Transgenic Zebrafish Larvae: A Calcium Imaging Tool to Study Drug Effects and Pathological Modeling2021

    • Author(s)
      Vicente Manuel、Salgado-Almario Jussep、Collins Michelle M.、Martinez-Sielva Antonio、Minoshima Masafumi、Kikuchi Kazuya、Domingo Beatriz、Llopis Juan
    • Journal Title

      Biomedicines

      Volume: 9 Issue: 10 Pages: 1294-1294

    • DOI

      10.3390/biomedicines9101294

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Anti-Siglec-15 antibody suppresses bone resorption by inhibiting osteoclast multinucleation without attenuating bone formation2021

    • Author(s)
      Tsukazaki Hiroyuki、Kikuta Junichi、Ao Tomoka、Morimoto Akito、Fukuda Chie、Tsuda Eisuke、Minoshima Masafumi、Kikuchi Kazuya、Kaito Takashi、Ishii Masaru
    • Journal Title

      Bone

      Volume: 152 Pages: 116095-116095

    • DOI

      10.1016/j.bone.2021.116095

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of Off-On Switching 19F MRI Probes for Cathepsin K Activity Detection2021

    • Author(s)
      Konishi Yuki、Okunishi Atsuya、Sugihara Fuminori、Nakamura Tatsuya、Akazawa Kazuki、Minoshima Masafumi、Kikuchi Kazuya
    • Journal Title

      Bulletin of the Chemical Society of Japan

      Volume: 94 Issue: 6 Pages: 1690-1694

    • DOI

      10.1246/bcsj.20210099

    • NAID

      130008066557

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Near-infrared fluorescent probes: a next-generation tool for protein-labeling applications2021

    • Author(s)
      Reja Shahi Imam、Minoshima Masafumi、Hori Yuichiro、Kikuchi Kazuya
    • Journal Title

      Chemical Science

      Volume: 12 Issue: 10 Pages: 3437-3447

    • DOI

      10.1039/d0sc04792a

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Optical Manipulation of Subcellular Protein Translocation Using a Photoactivatable Covalent Labeling System2021

    • Author(s)
      Kowada Toshiyuki、Arai Keisuke、Yoshimura Akimasa、Matsui Toshitaka、Kikuchi Kazuya、Mizukami Shin
    • Journal Title

      Angewandte Chemie International Edition

      Volume: 60 Issue: 20 Pages: 11378-11383

    • DOI

      10.1002/anie.202016684

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Fluorogenic probes for detecting deacylase and demethylase activity towards post-translationally-modified lysine residues2021

    • Author(s)
      Hori Yuichiro、Nishiura Miyako、Tao Tomomi、Baba Reisuke、Bull Steven D.、Kikuchi Kazuya
    • Journal Title

      Chemical Science

      Volume: 12 Issue: 7 Pages: 2498-2503

    • DOI

      10.1039/d0sc06551j

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A step towards gadolinium-free bioresponsive MRI contrast agent2021

    • Author(s)
      Wyskocka-Gajda Marzena、Przypis Lukasz、Olesiejuk Monika、Krawczyk Tomasz、Kuznik Anna、Nawara Krzysztof、Minoshima Masafumi、Sugihara Fuminori、Kikuchi Kazuya、Kuznik Nikodem
    • Journal Title

      European Journal of Medicinal Chemistry

      Volume: 211 Pages: 113086-113086

    • DOI

      10.1016/j.ejmech.2020.113086

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Single-cell dynamics of pannexin-1-facilitated programmed ATP loss during apoptosis2020

    • Author(s)
      Imamura Hiromi、Sakamoto Shuichiro、Yoshida Tomoki、Matsui Yusuke、Penuela Silvia、Laird Dale W、Mizukami Shin、Kikuchi Kazuya、Kakizuka Akira
    • Journal Title

      eLife

      Volume: 9

    • DOI

      10.7554/elife.61960

    • NAID

      120006893984

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] An Acid‐Activatable Fluorescence Probe for Imaging Osteocytic Bone Resorption Activity in Deep Bone Cavities2020

    • Author(s)
      Hashimoto Ryu、Minoshima Masafumi、Kikuta Junichi、Yari Shinya、Bull Steven D.、Ishii Masaru、Kikuchi Kazuya
    • Journal Title

      Angewandte Chemie International Edition

      Volume: 59 Issue: 47 Pages: 20996-21000

    • DOI

      10.1002/anie.202006388

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A Photodeactivatable Antagonist for Controlling CREB-Dependent Gene Expression2020

    • Author(s)
      Imoto Takuma、Minoshima Masafumi、Yokoyama Tatsushi、Emery Ben P.、Bull Steven D.、Bito Haruhiko、Kikuchi Kazuya
    • Journal Title

      ACS Central Science

      Volume: 6 Issue: 10 Pages: 1813-1818

    • DOI

      10.1021/acscentsci.0c00736

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Oxygen Functional Groups on MWCNT Surface as Critical Factor Boosting T2 Relaxation Rate of Water Protons: Towards Improved CNT-Based Contrast Agents2020

    • Author(s)
      Tomczyk Mateusz Michal、Boncel Slawomir、Herman Artur、Krawczyk Tomasz、Jakobik-Kolon Agata、Pawlyta Miroslawa、Krzywiecki Maciej、Chrobak Artur、Minoshima Masafumi、Sugihara Fuminori、Kikuchi Kazuya、Kuznik Nikodem
    • Journal Title

      International Journal of Nanomedicine

      Volume: 15 Pages: 7433-7450

    • DOI

      10.2147/ijn.s257230

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Rapid no-wash labeling of PYP-tag proteins with reactive fluorogenic ligands affords stable fluorescent protein conjugates for long-term cell imaging studies2020

    • Author(s)
      Kumar N, Hori, Y. Nishiura M, Kikuchi K
    • Journal Title

      Chem Sci

      Volume: 11 Issue: 14 Pages: 3694-3701

    • DOI

      10.1039/d0sc00499e

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of photoswitchable fluorescent molecules using arylazopyrazole2020

    • Author(s)
      Torii K, Hori Y, Watabe K, Kikuchi K
    • Journal Title

      Bull Chem Soc Jpn.

      Volume: - Issue: 7 Pages: 821-824

    • DOI

      10.1246/bcsj.20200077

    • NAID

      130007879560

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Development of Fluorogenic Probes for Rapid High-Contrast Imaging of Transient Nuclear Localization of Sirtuin 32020

    • Author(s)
      Gao J, Hori Y, Shimomura T, Bordy M, Hasserodt J, Kikuchi K
    • Journal Title

      Chembiochem

      Volume: 21 Issue: 5 Pages: 656-662

    • DOI

      10.1002/cbic.201900568

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Live-Cell Imaging of Protein Degradation Utilizing Designed Protein-Tag Mutant and Fluorescent Probe with Turn-Off Switch2020

    • Author(s)
      Gao J, Hori Y, Takeuchi O, Kikuchi K
    • Journal Title

      Bioconjug Chem

      Volume: 31 Issue: 3 Pages: 577-583

    • DOI

      10.1021/acs.bioconjchem.9b00696

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] In Vivo Multicolor Imaging with Fluorescent Probes Revealed the Dynamics and Function of Osteoclast Proton Pumps2019

    • Author(s)
      Minoshima Masafumi、Kikuta Junichi、Omori Yuta、Seno Shigeto、Suehara Riko、Maeda Hiroki、Matsuda Hideo、Ishii Masaru、Kikuchi Kazuya
    • Journal Title

      ACS Central Science

      Volume: 5 Issue: 6 Pages: 1059-1066

    • DOI

      10.1021/acscentsci.9b00220

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Photolytic Release of a Caged Inhibitor of an Endogenous Transcription Factor Enables Optochemical Control of CREB-Mediated Gene Expression2019

    • Author(s)
      Imoto Takuma、Kawase Akihiro、Minoshima Masafumi、Yokoyama Tatsushi、Bito Haruhiko、Kikuchi Kazuya
    • Journal Title

      Organic Letters

      Volume: 22 Issue: 1 Pages: 22-25

    • DOI

      10.1021/acs.orglett.9b03568

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] SCOTfluors: Small, Conjugatable, Orthogonal, and Tunable Fluorophores for In Vivo Imaging of Cell Metabolism2019

    • Author(s)
      Benson Sam、Fernandez Antonio、Barth Nicole D.、de Moliner Fabio、Horrocks Mathew H.、Herrington C. Simon、Abad Jose Luis、Delgado Antonio、Kelly Lisa、Chang Ziyuan、Feng Yi、Nishiura Miyako、Hori Yuichiro、Kikuchi Kazuya、Vendrell Marc
    • Journal Title

      Angewandte Chemie International Edition

      Volume: 58 Issue: 21 Pages: 6911-6915

    • DOI

      10.1002/anie.201900465

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Nano-particle based 19F MRI contrast agent with tunable chemical switches2021

    • Author(s)
      Kazuya Kikuchi
    • Organizer
      Pacifichem 2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] in vivo Imaging Probes to Clarify Cellular and Molecular Functions2020

    • Author(s)
      Kazuya Kikuchi
    • Organizer
      RSC Tokyo International Conferences 2020
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] New Biological Findings which were Revealed by Designed Fluorescent Probes2019

    • Author(s)
      Kikuchi Kazuya
    • Organizer
      Chemical Biology & Physiology Conference 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] In vivo Multicolor Imaging with Fluorescent Probes Revealed Dynamics and Function of Osteoclast Proton Pumps2019

    • Author(s)
      Kikuchi Kazuya
    • Organizer
      16th International, Methods & Applications of Fluorescence (Roger Y Tsien Memorial Symposium)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] In vivo Chemical Probes for MRI and Fluorescence Imaging2019

    • Author(s)
      Kikuchi Kazuya
    • Organizer
      ICBIC-19, International Conference on Biological Inorganic Chemistry
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Development of Multifunctional 19F MRI Contrast Agents Based on Fluorine-encapsulated Silica Nanoparticle2019

    • Author(s)
      Kikuchi Kazuya
    • Organizer
      The Future of Molecular MR: A Cellular and Molecular Imaging Workshop
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] イメージングプローブのデザイン・合成によるケミカルバイオロジー研究2019

    • Author(s)
      菊地 和也
    • Organizer
      第19回日本蛋白質科学会年会 第71回日本細胞生物学会大会 合同年次学会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Book] 先端の分析法 第2版(原理編第3章プローブ, MRIプローブ)2022

    • Author(s)
      蓑島維文、菊地和也
    • Total Pages
      1072
    • Publisher
      エヌ・ティー・エス
    • ISBN
      9784860437374
    • Related Report
      2021 Annual Research Report
  • [Book] 核酸科学ハンドブック(第5章2 MRIプローブ)2020

    • Author(s)
      蓑島維文、菊地和也
    • Total Pages
      576
    • Publisher
      講談社
    • ISBN
      9784065207864
    • Related Report
      2020 Research-status Report
  • [Patent(Industrial Property Rights)] ケージド化合物から化合物を放出させる方法2021

    • Inventor(s)
      蓑島維文、橋本 龍、菊地和也
    • Industrial Property Rights Holder
      蓑島維文、橋本 龍、菊地和也
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2021-022014
    • Filing Date
      2021
    • Related Report
      2020 Research-status Report

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Published: 2019-07-04   Modified: 2023-01-30  

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