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Development of screening method for lipid raft inhibitors

Research Project

Project/Area Number 18K19149
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 InstitutionKyushu University

Principal Investigator

Matsumori Nobuaki  九州大学, 理学研究院, 教授 (50314357)

Project Period (FY) 2018-06-29 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Keywords脂質ラフト / FRET / スフィンゴミエリン / スフィンゴミエリ / 阻害剤 / 蛍光
Outline of Final Research Achievements

Cell membranes have micro-domains called lipid rafts, but their physiological significance has yet to be clarified. On the other hand, enzyme inhibitors have been used not only as drugs but also as molecular probes for elucidating enzyme functions. Therefore, if a “raft inhibitor” that inhibits raft formation is available, it can be used as a molecular probe for exploring the function and properties of lipid rafts. In this study, we succeeded in developing an assay method for "raft inhibitors" by utilizing fluorescent lipids that selectively accumulate in raft or non-raft domains and observing the energy transfer between them. We also made this assay possible with artificial cell membranes and biological membranes, and succeeded in searching for new candidate compounds for raft inhibitors.

Academic Significance and Societal Importance of the Research Achievements

脂質ラフトは、各種タンパク質が特異的に集積することでシグナル伝達の“足場”として機能すると考えられているが、その生理的役割はまだ完全には解明されていない。そこで、本研究によりラフト阻害剤を分子プローブとしてラフト研究に供することができれば、ラフト形成の生理的意義をより明確にできると期待される。
また、脂質ラフトが生理的に重要な働きをしているとすると、ラフトを破壊する薬剤、すなわちラフト阻害剤は何らかの毒性や生理作用を示すはずである。したがって、本研究で開発したアッセイ法は、創薬における副作用スクリーニングとしても機能すると期待される。

Report

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

    (44 results)

All 2020 2019 2018 Other

All Int'l Joint Research (2 results) Journal Article (23 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 21 results,  Open Access: 7 results) Presentation (16 results) (of which Int'l Joint Research: 4 results) Book (1 results) Remarks (2 results)

  • [Int'l Joint Research] Abo Akademi University(フィンランド)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Abo Akademi University(フィンランド)

    • Related Report
      2018 Research-status Report
  • [Journal Article] The influence of ceramide and its dihydro analog on the physico-chemical properties of sphingomyelin bilayers2020

    • Author(s)
      Kinoshita Masanao、Tanaka Kaoru、Matsumori Nobuaki
    • Journal Title

      Chemistry and Physics of Lipids

      Volume: 226 Pages: 104835-104835

    • DOI

      10.1016/j.chemphyslip.2019.104835

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Total Synthesis of Amphidinol 3: A General Strategy for Synthesizing Amphidinol Analogues and Structure-Activity Relationship Study2020

    • Author(s)
      Wakamiya Yuma、Ebine Makoto、Matsumori Nobuaki、Oishi Tohru
    • Journal Title

      Journal of the American Chemical Society

      Volume: 142 Issue: 7 Pages: 3472-3478

    • DOI

      10.1021/jacs.9b11789

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chemical diversity and mode of action of natural products targeting lipids in the eukaryotic cell membrane2020

    • Author(s)
      Nishimura, S. & Matsumori, N.
    • Journal Title

      Nat. Prod. Rep.

      Volume: 37 Issue: 5 Pages: 677-702

    • DOI

      10.1039/c9np00059c

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Biophysics at Kyushu University2020

    • Author(s)
      Akiyama Ryo、Annaka Masahiko、Kohda Daisuke、Kubota Hiroyuki、Maeda Yusuke、Matsumori Nobuaki、Mizuno Daisuke、Yoshida Norio
    • Journal Title

      Biophysical Reviews

      Volume: 12 Issue: 2 Pages: 245-247

    • DOI

      10.1007/s12551-020-00643-2

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mechanism of local anesthetic-induced disruption of raft-like ordered membrane domains2019

    • Author(s)
      Kinoshita Masanao、Chitose Takeshi、Matsumori Nobuaki
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - General Subjects

      Volume: 1863 Issue: 9 Pages: 1381-1389

    • DOI

      10.1016/j.bbagen.2019.06.008

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cholesterol-Induced Conformational Change in the Sphingomyelin Headgroup2019

    • Author(s)
      Hanashima Shinya、Murakami Kazuhiro、Yura Michihiro、Yano Yo、Umegawa Yuichi、Tsuchikawa Hiroshi、Matsumori Nobuaki、Seo Sangjae、Shinoda Wataru、Murata Michio
    • Journal Title

      Biophysical Journal

      Volume: 117 Issue: 2 Pages: 307-318

    • DOI

      10.1016/j.bpj.2019.06.019

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Amphotericin B-Ergosterol Complex Spans a Lipid Bilayer as a Single-Length Assembly.2019

    • Author(s)
      Tomoya Yamamoto, Yuichi Umegawa, Hiroshi Tsuchikawa, Shinya Hanashima, Nobuaki Matsumori, Kosuke Funahashi, Sangjae Seo, Wataru Shinoda, Michio Murata.
    • Journal Title

      Biochemistry

      Volume: 58 Issue: 51 Pages: 5188-5196

    • DOI

      10.1021/acs.biochem.9b00835

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Perpendicular Orientation of Amphotericin B Methyl Ester in Hydrated Lipid Bilayers Supports the Barrel-Stave Model2019

    • Author(s)
      Yamamoto Tomoya、Umegawa Yuichi、Yamagami Masaki、Suzuki Taiga、Tsuchikawa Hiroshi、Hanashima Shinya、Matsumori Nobuaki、Murata Michio
    • Journal Title

      Biochemistry

      Volume: 印刷中 Issue: 17 Pages: 2282-2291

    • DOI

      10.1021/acs.biochem.9b00180

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Archaeal Glycolipid S-TGA-1 Is Crucial for Trimer Formation and Photocycle Activity of Bacteriorhodopsin2019

    • Author(s)
      Inada Masataka、Kinoshita Masanao、Matsumori Nobuaki
    • Journal Title

      ACS Chemical Biology

      Volume: 15 Issue: 1 Pages: 197-204

    • DOI

      10.1021/acschembio.9b00756

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Defining raft domains in the plasma membrane2019

    • Author(s)
      Akihiro Kusumi、Takahiro K. Fujiwara、Taka A. Tsunoyama、Rinshi S. Kasai、An‐An Liu、Koichiro M. Hirosawa、Masanao Kinoshita、Nobuaki Matsumori、Naoko Komura、Hiromune Ando、Kenichi G. N. Suzuki
    • Journal Title

      Traffic

      Volume: 21 Issue: 1 Pages: 106-137

    • DOI

      10.1111/tra.12718

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 天然物のNMR研究-立体化学決定および溶液中と膜中における配座解析2019

    • Author(s)
      松森信明
    • Journal Title

      NMR: Bulletin of the nuclear magnetic resonance society of Japan

      Volume: 10 Pages: 76-81

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A concise method for quantitative analysis of interactions between lipids and membrane proteins2019

    • Author(s)
      Inada Masataka、Kinoshita Masanao、Sumino Ayumi、Oiki Shigetoshi、Matsumori Nobuaki
    • Journal Title

      Analytica Chimica Acta

      Volume: 1059 Pages: 103-112

    • DOI

      10.1016/j.aca.2019.01.042

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Preparation and Membrane Distribution of Fluorescent Derivatives of Ceramide2019

    • Author(s)
      Matsufuji Takaaki、Kinoshita Masanao、Matsumori Nobuaki
    • Journal Title

      Langmuir

      Volume: 35 Issue: 6 Pages: 2392-2398

    • DOI

      10.1021/acs.langmuir.8b03176

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Theonellamide A, a marine-sponge-derived bicyclic peptide, binds to cholesterol in aqueous DMSO: Solution NMR-based analysis of peptide-sterol interactions using hydroxylated sterol2019

    • Author(s)
      Cornelio Kimberly、Espiritu Rafael Atillo、Hanashima Shinya、Todokoro Yasuto、Malabed Raymond、Kinoshita Masanao、Matsumori Nobuaki、Murata Michio、Nishimura Shinichi、Kakeya Hideaki、Yoshida Minoru、Matsunaga Shigeki
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - Biomembranes

      Volume: 1861 Issue: 1 Pages: 228-235

    • DOI

      10.1016/j.bbamem.2018.07.010

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] On the Importance of the C(1)-OH and C(3)-OH Functional Groups of the Long-Chain Base of Ceramide for Interlipid Interaction and Lateral Segregation into Ceramide-Rich Domains2018

    • Author(s)
      Mouts Anna、Vattulainen Elina、Matsufuji Takaaki、Kinoshita Masanao、Matsumori Nobuaki、Slotte J. Peter
    • Journal Title

      Langmuir

      Volume: 34 Issue: 51 Pages: 15864-15870

    • DOI

      10.1021/acs.langmuir.8b03237

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Sphingomyelin Stereoisomers Reveal That Homophilic Interactions Cause Nanodomain Formation2018

    • Author(s)
      Yano Yo、Hanashima Shinya、Yasuda Tomokazu、Tsuchikawa Hiroshi、Matsumori Nobuaki、Kinoshita Masanao、Al Sazzad Md. Abdullah、Slotte J. Peter、Murata Michio
    • Journal Title

      Biophysical Journal

      Volume: 115 Issue: 8 Pages: 1530-1540

    • DOI

      10.1016/j.bpj.2018.08.042

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Evidence of lipid rafts based on the partition and dynamic behavior of sphingomyelins2018

    • Author(s)
      Kinoshita Masanao、Suzuki Kenichi G.N.、Murata Michio、Matsumori Nobuaki
    • Journal Title

      Chemistry and Physics of Lipids

      Volume: 215 Pages: 84-95

    • DOI

      10.1016/j.chemphyslip.2018.07.002

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Synthesis and Stereochemical Revision of the C31-C67 Fragment of Amphidinol 32018

    • Author(s)
      Wakamiya Yuma、Ebine Makoto、Murayama Mariko、Omizu Hiroyuki、Matsumori Nobuaki、Murata Michio、Oishi Tohru
    • Journal Title

      Angewandte Chemie

      Volume: 130 Issue: 21 Pages: 6168-6172

    • DOI

      10.1002/ange.201712167

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Synthesis and Complete Structure Determination of a Sperm-Activating and -Attracting Factor Isolated from the Ascidian Ascidia sydneiensis2018

    • Author(s)
      Watanabe Tomohiro、Shibata Hajime、Ebine Makoto、Tsuchikawa Hiroshi、Matsumori Nobuaki、Murata Michio、Yoshida Manabu、Morisawa Masaaki、Lin Shu、Yamauchi Kosei、Sakai Ken、Oishi Tohru
    • Journal Title

      Journal of Natural Products

      Volume: 81 Issue: 4 Pages: 985-997

    • DOI

      10.1021/acs.jnatprod.7b01052

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Dynamic membrane interactions of antibacterial and antifungal biomolecules, and amyloid peptides, revealed by solid-state NMR spectroscopy2018

    • Author(s)
      Naito Akira、Matsumori Nobuaki、Ramamoorthy Ayyalusamy
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - General Subjects

      Volume: 1862 Issue: 2 Pages: 307-323

    • DOI

      10.1016/j.bbagen.2017.06.004

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Recent Solid-State NMR Studies of Hydrated Lipid Membranes2018

    • Author(s)
      Umegawa Yuichi、Matsumori Nobuaki、Murata Michio
    • Journal Title

      Annu. Rep. NMR Spectrosc.

      Volume: 94 Pages: 41-72

    • DOI

      10.1016/bs.arnmr.2017.12.003

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] 蛍光修飾したスフィンゴミエリン誘導体の脂質ラフト観察への応用2018

    • Author(s)
      木下 祥尚, 松森信明
    • Journal Title

      生物物理

      Volume: 58 Pages: 321-323

    • NAID

      130007522421

    • Related Report
      2018 Research-status Report
  • [Journal Article] 生体膜を標的にする天然有機化合物2018

    • Author(s)
      西村 慎一, 掛谷 秀昭, 松森信明
    • Journal Title

      化学と生物

      Volume: 56 Pages: 678-685

    • Related Report
      2018 Research-status Report
  • [Presentation] Development of novel fluorescent analogs of sphingomyelins, ceramide, and hybrid phosphatidylcholines.2019

    • Author(s)
      Takaaki Matsufuji, Kana Hirano, Yutaro Tajima, Masanao Kinoshita, and Nobuaki Matsumori
    • Organizer
      60th International Conference on the Bioscience of Lipids
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Effect of specific lipid interaction on membrane protein activities revealed by surface plasmon resonance analysis2019

    • Author(s)
      Masataka Inada,Masanao Kinoshita,Masayuki Iwamoto, Shigetoshi Oiki, Nobuaki Matsumori
    • Organizer
      60th International Conference on the Bioscience of Lipids
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Local anesthetic molecule dibucaine disrupts raft-like/non-raft-like phase separation formed in artificial membranes2019

    • Author(s)
      Masanao Kinoshita Takeshi Chitose and Nobuaki Matsumori
    • Organizer
      60th International Conference on the Bioscience of Lipids
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 膜タンパク質―脂質相互作用解析法の開発:脂質ケミカルバイオロジー創成に向けて2019

    • Author(s)
      稲田壮峰、木下祥尚、松森信明
    • Organizer
      日本ケミカルバイオロジー学会 第15回年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 脂質間FRETを用いたコントラストの強調とスフィンゴミエリンリッチ領域の可視化2019

    • Author(s)
      木下祥尚,阿野光,重富健太,村田道雄,池内順一,松森信明
    • Organizer
      日本化学会第99回春季年会
    • Related Report
      2018 Research-status Report
  • [Presentation] 低流量電子線散乱法を用いた局所的な脂質充填構造の解析2019

    • Author(s)
      山口晋平,木下祥尚, 松森信明
    • Organizer
      日本化学会第99回春季年会
    • Related Report
      2018 Research-status Report
  • [Presentation] アシル鎖長の異なるスフィンゴミエリンがドメイン形成に与える影響ー蛍光スフィンゴミエリンを用いた検討2019

    • Author(s)
      平野佳奈,木下祥尚, 松森信明
    • Organizer
      日本化学会第99回春季年会
    • Related Report
      2018 Research-status Report
  • [Presentation] 脂質膜内葉と外葉の非対称性が人工ラフト膜の構造や物性に与える影響2019

    • Author(s)
      古閑卓也,木下祥尚,松森信明
    • Organizer
      日本化学会第99回春季年会
    • Related Report
      2018 Research-status Report
  • [Presentation] 脂質固定ビーズによる脂質特異的タンパク質の同定2019

    • Author(s)
      安田裕貴, 松藤嵩明,木下祥尚,松森信明
    • Organizer
      日本化学会第99回春季年会
    • Related Report
      2018 Research-status Report
  • [Presentation] 人工膜脂質に対する吸入麻酔剤の作用2019

    • Author(s)
      川口翼,木下祥尚,松森信明
    • Organizer
      日本化学会第99回春季年会
    • Related Report
      2018 Research-status Report
  • [Presentation] Detailed insight for the effect of specific interaction with lipids on membrane protein activation2019

    • Author(s)
      Masataka Inada,Masanao Kinoshita,Masayuki Iwamoto,Shigetoshi Oiki,Nobuaki Matsumori
    • Organizer
      日本化学会第99回春季年会
    • Related Report
      2018 Research-status Report
  • [Presentation] Crucial Role of Specific Interactions with Archeal Glycolipid S-TGA-1 in Structuralization and Functionalization of Bacteriorhodopsin2018

    • Author(s)
      Masataka Inada,Masanao Kinoshita,Nobuaki Matsumori
    • Organizer
      第56回日本生物物理学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] 膜タンパク質-脂質相互作用に対する定量評価法の開発および特異的脂質の同定2018

    • Author(s)
      稲田壮峰,木下祥尚,松森信明
    • Organizer
      日本分析化学会第67年会
    • Related Report
      2018 Research-status Report
  • [Presentation] 異なるアシル鎖をもつ蛍光スフィンゴミエリの調製とドメイン形成の解析2018

    • Author(s)
      野佳奈,木下祥尚,松森信明
    • Organizer
      第12回バイオ関連化学シンポジウム
    • Related Report
      2018 Research-status Report
  • [Presentation] 脂質膜中における膜作用性海洋天然物アンフィジノール3とステロールの相互作用2018

    • Author(s)
      檜枝愛美, 木下祥尚,松森信明
    • Organizer
      第12回バイオ関連化学シンポジウム
    • Related Report
      2018 Research-status Report
  • [Presentation] Development of a concise method for quantitative analysis of interactions between membrane proteins2018

    • Author(s)
      Masataka Inada,Masanao Kinoshita,Nobuaki Matsumori
    • Organizer
      International Workshop on Biological Membranes : Tiny Lipids With Grand Function
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Book] 天然物の化学Ⅱ(科学のとびら64)2018

    • Author(s)
      上村 大輔  編
    • Total Pages
      192
    • Publisher
      東京化学同人
    • ISBN
      9784807915057
    • Related Report
      2018 Research-status Report
  • [Remarks] 九州大学大学院理学研究院化学部門 生体分析化学研究室

    • URL

      http://www.scc.kyushu-u.ac.jp/BioanalChem/index.html

    • Related Report
      2019 Annual Research Report
  • [Remarks] 九州大学大学院理学研究院化学部門 生体分析化学研究室

    • URL

      http://www.scc.kyushu-u.ac.jp/BioanalChem/

    • Related Report
      2018 Research-status Report

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Published: 2018-07-25   Modified: 2021-02-19  

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