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Development of ligand screening using chemical array and membrane protein-expressed cells

Research Project

Project/Area Number 18K05366
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 InstitutionInstitute of Physical and Chemical Research

Principal Investigator

Kondoh Yasumitsu  国立研究開発法人理化学研究所, 環境資源科学研究センター, 専任研究員 (80333342)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsケミカルアレイ / 膜結合蛋白質 / リガンド / ハイスループットスクリーニング / 膜受容体 / 細胞
Outline of Final Research Achievements

Chemical array was developed as a high-throughput screening technique for compounds that bind to target proteins by immobilizing compounds on glass slides. In order to establish the basic processing conditions for cell binding assays using membrane-bound proteins as targets, I examined various conditions in the chemical array and SPR imaging methods. In parallel, I also established screening conditions using intracellular calcium ion assay, and searched for natural products that enhance the response of receptors, and found that certain plant extracts had an enhancing effect.

Academic Significance and Societal Importance of the Research Achievements

GPCRのリガンド探索系としては、RIラベルされたリガンドを用いた結合アッセイや、細胞内のcAMPやCa2+濃度などシグナル伝達の下流に着目した活性測定の系が知られているが、いずれも高価な機器や試薬が必要であり、また、リガンド探索の際にライブラリー化合物を全てRIラベルすることは不可能である。これらの手法に代わるハイスループットなリガンド探索系が必要である。また、受容体の応答を増強する植物抽出物については、今後、活性本体の構造を決定することにより、その受容体で初めて見出した天然の応答増強物質として特許出願、論文発表をすることができる。

Report

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

    (37 results)

All 2021 2020 2019 2018

All Journal Article (14 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 14 results,  Open Access: 10 results) Presentation (23 results) (of which Int'l Joint Research: 5 results)

  • [Journal Article] Discovery of small-molecule modulator of heterotrimeric Gi-protein by integrated phenotypic profiling and chemical proteomics2020

    • Author(s)
      16)Kawamura, T., Futamura, Y., Shang, E., Muroi, M., Janning, P., Ueno, M., Wilke, J., Takeda, S., Kondoh, Y., Ziegler, S., Watanabe, N., Waldmann, H., Osada, H.
    • Journal Title

      Biosci. Biotechnol. Biochem.

      Volume: 84 Issue: 12 Pages: 2484-2490

    • DOI

      10.1080/09168451.2020.1812375

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Pesticide treatment reduces hydrophobic pollutant contamination in Cucurbita pepo through competitive binding to major latex-like proteins.2020

    • Author(s)
      Fujita K, Kondoh Y, Honda K, Haga Y, Osada H, Matsumura C, Inui H.
    • Journal Title

      Environ Pollut

      Volume: 266 Pages: 115179-115179

    • DOI

      10.1016/j.envpol.2020.115179

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Interaction between goniothalamin and peroxisomal multifunctional enzyme type 2 triggering endoplasmic reticulum stress2020

    • Author(s)
      Sophonnithiparasert T, Aruksakunwong O, Tashiro E, Kondoh Y, Muroi M, Osada H, Imoto M, Watanapokasin R
    • Journal Title

      Heliyon

      Volume: 6 Issue: 10 Pages: e05200-e05200

    • DOI

      10.1016/j.heliyon.2020.e05200

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Miclxin, a novel MIC60 inhibitor, induces apoptosis via mitochondrial stress in β-catenin mutant tumor cells.2020

    • Author(s)
      20)Ikeda, H., Muroi, M., Kondoh, Y., Ishikawa, S., Kakeya, H., Osada, H., Imoto, M.
    • Journal Title

      ACS Chem. Biol.

      Volume: 15 Issue: 8 Pages: 2195-2204

    • DOI

      10.1021/acschembio.0c00381

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inhibition of mitochondrial complex I by the novel compound FSL0260 enhances high salinity-stress tolerance in Arabidopsis thaliana2020

    • Author(s)
      Sako Kaori、Futamura Yushi、Shimizu Takeshi、Matsui Akihiro、Hirano Hiroyuki、Kondoh Yasumitsu、Muroi Makoto、Aono Harumi、Tanaka Maho、Honda Kaori、Shimizu Kenshirou、Kawatani Makoto、Nakano Takeshi、Osada Hiroyuki、Noguchi Ko、Seki Motoaki
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 8691-8691

    • DOI

      10.1038/s41598-020-65614-9

    • NAID

      120006876594

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of Target Protein for Bio-active Small Molecule Using Photo-cross Linked Beads and MALDI-TOF Mass Spectrometry2020

    • Author(s)
      Suvarna Kruthi、Honda Kaori、Muroi Makoto、Kondoh Yasumitsu、Watanabe Nobumoto、Osada Hiroyuki
    • Journal Title

      BIO-PROTOCOL

      Volume: 10 Issue: 3

    • DOI

      10.21769/bioprotoc.3517

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Measurement of ATPase Activity of Valosin-containing Protein/p972020

    • Author(s)
      Suvarna Kruthi、Honda Kaori、Muroi Makoto、Kondoh Yasumitsu、Osada Hiroyuki、Watanabe Nobumoto
    • Journal Title

      BIO-PROTOCOL

      Volume: 10 Issue: 3

    • DOI

      10.21769/bioprotoc.3516

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Abscisic Acid Derivatives with Different Alkyl Chain Lengths Activate Distinct Abscisic Acid Receptor Subfamilies2019

    • Author(s)
      Yoshida Kazuko、Kondoh Yasumitsu、Iwahashi Fukumatsu、Nakano Takeshi、Honda Kaori、Nagano Eiki、Osada Hiroyuki
    • Journal Title

      ACS Chemical Biology

      Volume: 14 Issue: 9 Pages: 1964-1971

    • DOI

      10.1021/acschembio.9b00453

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Mechanism of Action of Prethioviridamide, an Anticancer Ribosomally Synthesized and Post-Translationally Modified Peptide with a Polythioamide Structure2019

    • Author(s)
      Takase Shohei、Kurokawa Rumi、Kondoh Yasumitsu、Honda Kaori、Suzuki Takehiro、Kawahara Teppei、Ikeda Haruo、Dohmae Naoshi、Osada Hiroyuki、Shin-ya Kazuo、Kushiro Tetsuo、Yoshida Minoru、Matsumoto Ken
    • Journal Title

      ACS Chemical Biology

      Volume: 14 Issue: 8 Pages: 1819-1828

    • DOI

      10.1021/acschembio.9b00410

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of Mirror-Image Screening Systems for XIAP BIR3 Domain Inhibitors2019

    • Author(s)
      Shu Keitou、Iwamoto Naoya、Honda Kaori、Kondoh Yasumitsu、Hirano Hiroyuki、Osada Hiroyuki、Ohno Hiroaki、Fujii Nobutaka、Oishi Shinya
    • Journal Title

      Bioconjugate Chemistry

      Volume: 30 Issue: 5 Pages: 1395-1404

    • DOI

      10.1021/acs.bioconjchem.9b00154

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Identification of a chemical modulator of EZH2-mediated silencing by cell-based high-throughput screening assay2019

    • Author(s)
      Murashima Akihiro、Shinjo Keiko、Katsushima Keisuke、Onuki Tetsuo、Kondoh Yasumitsu、Osada Hiroyuki、Kagaya Noritaka、Shin-ya Kazuo、Kimura Hiroshi、Yoshida Minoru、Murakami Shingo、Kondo Yutaka.
    • Journal Title

      The Journal of Biochemistry

      Volume: - Issue: 1 Pages: 1-10

    • DOI

      10.1093/jb/mvz007

    • NAID

      40021952184

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A small-molecule ligand of valosin-containing protein/p97 inhibits cancer cell-accelerated fibroblast migration.2019

    • Author(s)
      Suvarna K, Honda K, Muroi M, Kondoh Y, Osada H, Watanabe N
    • Journal Title

      J Biol Chem

      Volume: 294 Issue: 9 Pages: 2988-2996

    • DOI

      10.1074/jbc.ra118.004741

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chemical array system, a platform to identify novel hepatitis B virus entry inhibitors targeting sodium taurocholate cotransporting polypeptide2018

    • Author(s)
      Kaneko M, Futamura Y, Tsukuda S, Kondoh Y, Sekine T, Hirano H, Fukano K, Ohashi H, Saso W, Morishita R, Matsunaga S, Kawai F, Ryo A, Park S-Y, Suzuki R, Aizaki H, Ohtani N, Sureau C, Wakita T, Osada H, Watashi K
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 2769-2769

    • DOI

      10.1038/s41598-018-20987-w

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Identification of a small-molecule ligand of β-arrestin1 as an inhibitor of stromal fibroblast cell migration accelerated by cancer cells2018

    • Author(s)
      Suvarna K, Honda K, Kondoh Y, Osada H, Watanabe N.
    • Journal Title

      Cancer Med

      Volume: 7 Issue: 3 Pages: 883-893

    • DOI

      10.1002/cam4.1339

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 汚染物質輸送因子Major latex-like proteinの遺伝子発現と結合活性の制御によるウリ科作物汚染の低減化2021

    • Author(s)
      藤田健太郎、近藤恭光、本田香織、羽賀雄紀、長田裕之、松村千里、乾秀之
    • Organizer
      日本農薬学会第46回大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Comprehensive detection of RNA targets that bind to chemical compounds using next-generation sequencing and data-driven method.2020

    • Author(s)
      Hayate Fujimoto, Yasumitsu Kondoh, Tatsuro Kawamura, Sumitaka Hase, Masaya Imoto, Hiroyuki Osada, Yasubumi Sakakibara
    • Organizer
      RNA 2020 Meeting
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 統合表現型プロファイリングとケミカルプロテオミクスの手法による3量体Giタンパク質調節化合物の発見2020

    • Author(s)
      河村達郎、二村友史、Erchang Shang、室井誠、Petra Janning、上野雅佳、Julian Wilke、武田茂樹、近藤恭光、Slava Ziegler、渡辺信元、Herbert Waldmann、長田裕之
    • Organizer
      日本農芸化学会2020年度大会
    • Related Report
      2019 Research-status Report
  • [Presentation] ウリ科作物の新規汚染低減化法の開発2019

    • Author(s)
      藤田健太郎、近藤恭光、本田香織、羽賀雄紀、長田裕之、松村千里、乾秀之
    • Organizer
      神戸大学研究基盤センター若手フロンティア研究会2019
    • Related Report
      2019 Research-status Report
  • [Presentation] 汚染物質輸送因子の遺伝子発現と結合活性制御によるウリ科作物における作物汚染の低減化2019

    • Author(s)
      藤田健太郎、近藤恭光、本田香織、羽賀雄紀、長田裕之、松村千里、乾秀之
    • Organizer
      第37回農薬環境科学研究会
    • Related Report
      2019 Research-status Report
  • [Presentation] 受容体特異的な3′-alkyl ABAを用いたアブシジン酸受容体機能解析2019

    • Author(s)
      由田和津子、近藤恭光、岩橋福松、中野雄司、本田香織、永野栄喜、長田裕之
    • Organizer
      植物化学調節学会第54回大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Reduction of pop contamination in Cucurbitaceae family focusing on the transporting factors for POPs by the treatment of pesticides2019

    • Author(s)
      Fujita K, Kondoh Y, Honda K, Osada H, Inui H
    • Organizer
      39th International Symposium on Halogenated Persistent Organic Pollutants: DioXin 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Identification and characterization of small-molecular compounds that inhibit salicylic acid-mediated signaling pathway in Arabidopsis2019

    • Author(s)
      Nobuaki Ishihama, Yoshiteru Noutoshi, Seung-won Choi, Ivana Saska, Shuta Asai, Kaori Takizawa, Yasumitsu Kondoh, Yuko Nomura, Hirofumi Nakagami, Hiroyuki Osada, Ken Shirasu
    • Organizer
      IS-MPMI XVIII Congress
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Selective activation of abscisic acid receptors by 3’-alkyl ABAs2019

    • Author(s)
      Kazuko Yoshida, Yasumitsu Kondoh, Fukumatsu Iwahashi, Takeshi Nakano, Kaori Honda, Eiki Nagano, Hiroyuki Osada.
    • Organizer
      Chemical Probe Workshop
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 受容体特異的な3’-alkyl ABAを用いたABA受容体機能解析 1.構造活性相関2019

    • Author(s)
      由田和津子、近藤恭光、岩橋福松、中野雄司、本田香織、永野栄喜、長田裕之
    • Organizer
      日本農芸化学会2019年度大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 受容体特異的な3’-alkyl ABAを用いたABA受容体機能解析 2.ドッキングシミュレーション2019

    • Author(s)
      近藤恭光、由田和津子、岩橋福松、中野雄司、本田香織、永野栄喜、長田裕之
    • Organizer
      日本農芸化学会2019年度大会
    • Related Report
      2018 Research-status Report
  • [Presentation] がん細胞に活性酸素種産生を誘導する化合物RKN9055の発見と作用解析2019

    • Author(s)
      河村 達郎、二村 友史、室井 誠、川谷 誠、SHANG Erchang、JANNING Petra、近藤 恭光、野川 俊彦、ZIEGLER Slava、渡辺 信元、WALDMANN Herbert、長田 裕之
    • Organizer
      日本農芸化学会2019年度大会
    • Related Report
      2018 Research-status Report
  • [Presentation] XIAP BIR3ドメインの化学合成と鏡像スクリーニングへの応用2019

    • Author(s)
      岩本 直也、周敬棠、本田香織、近藤恭光、長田裕之、井貫晋輔、大野浩章、藤井信孝、大石真也
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Research-status Report
  • [Presentation] 汚染物質輸送因子の結合活性制御に着目したウリ科作物の汚染低減化2019

    • Author(s)
      藤田健太郎、近藤恭光、本田香織、羽賀雄紀、長田裕之、松村千里、乾秀之
    • Organizer
      日本農薬学会第44回大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Target identification of a small-molecule that inhibits cancer cell-accelerated fibroblast migration2019

    • Author(s)
      Kruthi Suvarna, Kaori Honda, Makoto Muroi, Yasumitsu Kondoh, Hiroyuki Osada, Nobumoto Watanabe
    • Organizer
      The 5th CSRS-ITbM Joint Workshop
    • Related Report
      2018 Research-status Report
  • [Presentation] ケミカルバイオロジーからアプローチしたTAZの新しい制御機構の解析2018

    • Author(s)
      長島俊太、丸山順一、岩佐宏晃、有本-松崎京子、本田 香織、近藤恭光、長田裕之、名和眞希子、石上-湯浅磨里、影近弘之、中浜健一、仁科博史、畑裕
    • Organizer
      MBSJ日本分子生物学会
    • Related Report
      2018 Research-status Report
  • [Presentation] A small-molecule ligand of VCP inhibits accelerated fibroblast migration by cancer cells2018

    • Author(s)
      Kruthi Suvarna, Kaori Honda, Makoto Muroi, Yasumitsu Kondoh, Hiroyuki Osada, Nobumoto Watanabe
    • Organizer
      MBSJ日本分子生物学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 植物成長促進化合物PPGによる植物カルス形成制御機構の解明2018

    • Author(s)
      前川琴美、田中翔太、竹野駿、山上あゆみ、筧 雄介、嶋田幸久、近藤恭光、堂前 直、嶋田勢津子、松井 南、久城哲夫、長田裕之、浅見忠男、篠崎一雄、中野雄司
    • Organizer
      第53回植物化学調節学会年次大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 植物免疫阻害剤を用いた植物免疫応答制御因子の探索2018

    • Author(s)
      石濱伸明, 能年義輝, 崔 勝媛, Ivana Saska, 浅井秀太, 瀧澤 香, 野村有子, 中神弘史, 近藤恭光, 長田裕之, 白須 賢
    • Organizer
      平成30年度日本植物病理学会関東部会
    • Related Report
      2018 Research-status Report
  • [Presentation] Reduction of crop contamination resulting from hydrophobic contaminants by the treatment of pesticides targeting to its transport factors2018

    • Author(s)
      Fujita K, Sakai A, Kondoh Y, Honda K, Osada H, Inui H
    • Organizer
      38th International Symposium on Halogenated Persistent Organic Pollutants & 10th International PCB Workshop
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] JBIR-140 の細胞増殖抑制機構の解析2018

    • Author(s)
      松本 健、高瀬翔平、近藤恭光、鈴木健裕、堂前直、新家一男、長田裕之、久城哲夫、吉田稔
    • Organizer
      日本ケミカルバイオロジー学会第13回年会
    • Related Report
      2018 Research-status Report
  • [Presentation] 高脂溶性汚染物質によって引き起こされる作物汚染の化合物輸送因子を標的とした農薬による低減化2018

    • Author(s)
      藤田健太郎、酒井葵衣、近藤恭光、本田香織、長田裕之、乾秀之
    • Organizer
      日本農薬学会第43回大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 新規インスリン分泌促進化合物の分子機構の解明2018

    • Author(s)
      松永 耕一、牛込剛史、近藤恭光、本田香織、長田裕之、泉 哲郎
    • Organizer
      第61回日本糖尿病学会年次学術集会
    • Related Report
      2018 Research-status Report

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

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