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Search for marine natural products that act on "cellular machinery" on cell surface

Research Project

Project/Area Number 15H04546
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Aquatic life science
Research InstitutionHokkaido University

Principal Investigator

Sakai Ryuichi  北海道大学, 水産科学研究院, 教授 (20265721)

Co-Investigator(Kenkyū-buntansha) 東田 千尋  富山大学, 和漢医薬学総合研究所, 教授 (10272931)
及川 雅人  横浜市立大学, 生命ナノシステム科学研究科(八景キャンパス), 教授 (70273571)
Project Period (FY) 2015-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2018: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2017: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2016: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2015: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
Keywords海綿 / ホヤ / 神経受容体 / 毒素 / タンパク質 / ペプチド / アルカロイド / 海洋天然物 / シナプス受容体 / グアニジンアルカロイド / トロンボポエチン / ペプチド毒 / サイトカイン / ドラッグデリバリ / ポリアミン / 膜透過 / 分子送達 / 糖鎖 / ビオプテリン / グルタミン酸受容体 / 生理活性 / 細胞内送達 / ドラッグデリバリー / 神経修復 / 生理活性物質 / 海洋生物 / 生理活性タンパク質 / 細胞膜
Outline of Final Research Achievements

Ion channels, receptors, sugar chains, etc. embedded in the cell membrane surface serve as the window for information exchange between cells, and can be regarded as "cellular machinery" that maintains homeostasis of multicellular organisms. In this study, we found novel compounds that act on synaptic receptors such as serotonin receptor, opioid receptor and glutamate receptor from water-soluble extracts of marine organisms. In addition to this, we also found peptide toxins, protein toxins and low molecular weight compounds that penetrate the cell membrane to enter cells despite being water soluble molecule. These results demonstrated that water soluble extract of marine organisms is an excellent source for not only neuroactive substances but also molecules that attack biological membranes act as cell barriers. These molecules are likely to have structural units that contribute to the development of drug delivery systems.

Academic Significance and Societal Importance of the Research Achievements

本研究で得られた神経活性物質は、脳神経伝達の調整に重要な役割を持つセロトニン受容体やオピオイド受容体に作用する新規の化合物である.この知見は、受容体に作用するに必要な化学構造の情報を提供し、未知の神経機能の解明、さらには神経疾患治療薬の開発につながる.また、本研究で得られたタンパク質毒素は細胞表面から細胞内に侵入し、核まで到達する.このような機能をうまく生かすことで、薬物や遺伝子を核内に届ける技術の開発につながる.本研究の成果は海洋生物資源の高度利用をさらに推進する基盤を築くものである.

Report

(5 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (31 results)

All 2019 2018 2017 2016 2015

All Journal Article (14 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 13 results,  Open Access: 4 results,  Acknowledgement Compliant: 3 results) Presentation (16 results) (of which Int'l Joint Research: 5 results,  Invited: 4 results) Book (1 results)

  • [Journal Article] Soritesidine, a Novel Proteinous Toxin from the Okinawan Marine Sponge Spongosorites sp.2019

    • Author(s)
      Sakai Ryuichi、Tanano Kota、Ono Takumi、Kitano Masaya、Iida Yusuke、Nakano Koji、Jimbo Mitsuru
    • Journal Title

      Marine Drugs

      Volume: 17 Issue: 4 Pages: 216-216

    • DOI

      10.3390/md17040216

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A novel sponge-derived protein thrombocorticin is a new agonist for thrombopoietin receptor2019

    • Author(s)
      Watari Hiromi、Nakajima Hiroya、Atsuumi Wataru、Nakamura Takanori、Nanya Takeshi、Ise Yuji、Sakai Ryuichi
    • Journal Title

      Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology

      Volume: 221 Pages: 82-88

    • DOI

      10.1016/j.cbpc.2019.04.003

    • NAID

      120006864488

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] An efficient enantiospecific synthesis of neuroactive glutamate analogues2019

    • Author(s)
      Shuntaro Tsukamoto, Hiyori Itagaki, Kenji Morokuma, Kei Miyako, Yuichi Ishikawa, Ryuichi Sakai, Masato Oikawa1
    • Journal Title

      Heterocycles

      Volume: 101

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] KB343, a Cyclic Tris-guanidine Alkaloid from Palauan Zoantharian Epizoanthus illoricatus2018

    • Author(s)
      Ken Matsumura, Tohru Taniguchi, James D. Reimer, Shuntaro Noguchi, Masaki J. Fujita, and Ryuichi Sakai
    • Journal Title

      Org. Lett.

      Volume: 20 Issue: 10 Pages: 3039-3043

    • DOI

      10.1021/acs.orglett.8b01069

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Studies on Aculeines: Synthetic Strategy to the Fully Protected Protoaculeine B, the N‐Terminal Amino Acid of Aculeine B2018

    • Author(s)
      塩﨑宏樹、宮原正義、大塚一憲、宮古圭、本田彬人、高崎祐一、高見澤聡、塚田秀行、石川裕一、酒井隆一、及川雅人
    • Journal Title

      Organic Letters

      Volume: 20 Issue: 11 Pages: 3403-3407

    • DOI

      10.1021/acs.orglett.8b01331

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 海綿の長鎖ポリアミン2018

    • Author(s)
      酒井隆一、松永智子
    • Journal Title

      ポリアミン

      Volume: 5 Pages: 5-13

    • Related Report
      2018 Annual Research Report
    • Open Access / Int'l Joint Research
  • [Journal Article] Prins Reaction Using Trioxane for Trisubstituted, cis-Fused Hexahydro-2H-furo[3,2-b]pyran Derivative2018

    • Author(s)
      Oriel Hlokoane, Hiyori Itagaki, Manami Chiba, Taiki Noda, Yuichi Takasaki, Kei Miyako, Ryuichi Sakai, Yuichi Ishikawa,* and Masato Oikawa
    • Journal Title

      Heterocycles

      Volume: 96 Issue: 3 Pages: 453-460

    • DOI

      10.3987/com-17-13776

    • NAID

      40021512805

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Isolation, Amino Acid Sequences, and Plausible Functions of the Galacturonic Acid-Binding Egg Lectin of the Sea Hare Aplysia kurodai2017

    • Author(s)
      Motohashi, S., Jimbo, M., Naito, T., Suzuki, T., Sakai, R., Kamiya, H.
    • Journal Title

      Marine drugs

      Volume: 15 Issue: 6 Pages: 161-161

    • DOI

      10.3390/md15060161

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Crystal structure of octocoral lectin SLL-2 complexed with Forssman antigen tetrasaccharide2017

    • Author(s)
      Akiko Kita, Mitsuru Jimbo, Ryuichi Sakai, Yukio Morimoto, Ryota Takeuchi, Hiroshi Tanaka, Takashi Takahashi, Kunio Miki
    • Journal Title

      Glycobiology

      Volume: 27 Issue: 8 Pages: 696-700

    • DOI

      10.1093/glycob/cwx043

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Two New Mycosporine-like Amino Acids LC-343 and Mycosporine-ethanolamine from the Micronesian Marine Sponge Lendenfeldia chondrodes2017

    • Author(s)
      Oda, Y., Zhang, Q., Matsunaga, S., Fujita, M. J., Sakai, R.
    • Journal Title

      Chemistry Letters

      Volume: 46 Issue: 8 Pages: 1272-1274

    • DOI

      10.1246/cl.170490

    • NAID

      130005906967

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] N-Methyl-β-carbolinium Salts and an N-Methylated 8-Oxoisoguanine as Acetylcholinesterase Inhibitors from a Solitary Ascidian, Cnemidocarpa irene2017

    • Author(s)
      Yohei Tadokoro, Teruaki Nishikawa, Taichi Ichimori, Satoko Matsunaga, Masaki J Fujita, Ryuichi Sakai
    • Journal Title

      ACS Omega

      Volume: 2 Issue: 3 Pages: 1074-1080

    • DOI

      10.1021/acsomega.7b00127

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Three-Component, Diastereoselective Prins-Ritter Reaction for cis-Fused 4-Amidotetrahydropyrans toward a Precursor for Possible Neuronal Receptor Ligands2016

    • Author(s)
      Manami Chiba, Yuichi Ishikawa, Ryuichi Sakai, and Masato Oikawa
    • Journal Title

      ACS combnatorial science

      Volume: 18 Issue: 7 Pages: 399-404

    • DOI

      10.1021/acscombsci.6b00046

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] A monocyclic neodysiherbaine analog: Synthesis and evaluation2016

    • Author(s)
      Koichi Fukushima, Yuichi Ishikawa, Ryuichi Sakai, Masato Oikawa
    • Journal Title

      Bioorganic & Medicinal Chemistry Letters

      Volume: 21 Issue: 21 Pages: 5164-5167

    • DOI

      10.1016/j.bmcl.2016.09.074

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mellpaladines and dopargimine, novel neuroactive guanidine alkaloids from a Palauan Didemnidae tunicate2016

    • Author(s)
      Hajime Uchimasu, Ken Matsumura, Masashi Tsuda, Keiko Kumagai, Mai Akakabe, Masaki J Fujita, Ryuichi Sakai
    • Journal Title

      Tetrahedron

      Volume: 72 Issue: 45 Pages: 7085-7193

    • DOI

      10.1016/j.tet.2016.09.051

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] 海綿由来蛋白質ThCによるトロンボポエチン受容体の活性化機構2019

    • Author(s)
      辺浩美、中島寛弥、渥海航、酒井隆一
    • Organizer
      平成31年度日本水産学会春季大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] パラオ産Epizoanthus illoricatusより得られた新規トリスグアニジンアルカロイドの構造と生理活性2018

    • Author(s)
      松村賢、谷口透、J. Reimer, 野口峻太朗、藤田雅紀、酒井隆一
    • Organizer
      第60回天然有機化合物討論会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 細胞表面の「生命装置」に作用する水溶性海洋天然物の探索(低分子編)2018

    • Author(s)
      酒井隆一
    • Organizer
      天然薬物の開発と応用シンポジウム講演要旨集 22nd 1‐4
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 単体ボヤCnemidocarpa ireneより得られた芳香族化合物の構造と機能2018

    • Author(s)
      宮古圭、保野洋子、品田哲郎、藤田雅紀、酒井隆一
    • Organizer
      平成30年度日本水産学会春季大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 西表産Spongosorites属海綿由来の新規タンパク質毒素の作用機構2018

    • Author(s)
      飯田祐介、中野宏治、上田拓也、北野雅也、藤田雅紀、酒井隆一
    • Organizer
      平成30年度日本水産学会春季大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] パラオ産Didemnidae科ホヤに含まれる新規神経活性物質グアニジンアルカロイドとその関連化合物に関する研究2017

    • Author(s)
      松村賢、内舛肇、藤田雅紀、酒井隆一、津田正史、熊谷慶子、赤壁麻衣
    • Organizer
      日本水産学会春季大会
    • Place of Presentation
      東京海洋大学(東京都港区)
    • Year and Date
      2017-03-26
    • Related Report
      2016 Annual Research Report
  • [Presentation] Bioactive metabolites from water-soluble marine extracts.2017

    • Author(s)
      Ryuichi Sakai
    • Organizer
      American Society of Pharmacognosy
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] A novel sponge-derived protein Thrombocorticin with thrombopoietin-like activity2017

    • Author(s)
      Hiromi Watari, Hiroya Nakajima, Wataru Atsuumi, Takanori Nakamura, Takeshi Nanya Masaki J Fujita, Ryuichi Sakai
    • Organizer
      International Symposium: Fisheries Science for Future Generations
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Novel guanidine alkaloids from an aqueous extract of Palauan Epizoanthus sp2017

    • Author(s)
      Ken Matsumura, Masaki J Fujita, James Reimer, Ryuichi Sakai
    • Organizer
      International Symposium: Fisheries Science for Future Generations
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Bioactive alkaloids from a solitary ascidian Cnemidocarpa irene2017

    • Author(s)
      Kei Miyako, Youhei Tadokoro, Taichi Ichimori, Masaki J Fujita, Ryuichi Sakai
    • Organizer
      International Symposium: Fisheries Science for Future Generations
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 単体ボヤCnemidocarpa ireneに含まれる生理活性アルカロイドの探索2017

    • Author(s)
      宮古圭、田所洋平、市森大地、藤田雅紀、酒井隆一
    • Organizer
      第59回天然有機化合物討論会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Soritesidine: A potent protein toxin from the marine sponge Spongosorites sp2016

    • Author(s)
      Ryuichi Sakai
    • Organizer
      US-JAPAN symposium on marine natural products
    • Place of Presentation
      ハワイ大学癌研究所 米国 ホノルル市
    • Year and Date
      2016-11-14
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 西表島産Spongosorites属海綿に含まれるタンパク質毒素の分離2016

    • Author(s)
      酒井隆一, 中野宏治, 上田拓也, 北野雅也, 小野 巧, 棚野豪太, 神保 充, 藤田雅紀
    • Organizer
      平成28年度日本水産学会年会
    • Place of Presentation
      東京海洋大学、(東京都、港区)
    • Year and Date
      2016-03-26
    • Related Report
      2015 Annual Research Report
  • [Presentation] 北海道産単体ボヤCnemidcarpa ireneに含まれる生理活性物質に関する研究2016

    • Author(s)
      田所洋平、酒井隆一、西川輝明、藤田雅紀
    • Organizer
      平成28年度日本水産学会年会
    • Place of Presentation
      東京海洋大学 (東京都、港区)
    • Year and Date
      2016-03-26
    • Related Report
      2015 Annual Research Report
  • [Presentation] パラオ産 Didemnidae科ホヤ由来新規神経活性化合物群Mellpaladine類に関 する研究2015

    • Author(s)
      内升 肇、松村 賢、津田 正史、熊谷 慶子、赤壁 舞依、藤田雅紀、酒井隆一
    • Organizer
      第57回天然有機化合物討論会
    • Place of Presentation
      神奈川県民ホール (神奈川県、横浜市)
    • Year and Date
      2015-09-07
    • Related Report
      2015 Annual Research Report
  • [Presentation] 海綿毒素ソリテシジンの研究2015

    • Author(s)
      酒井隆一
    • Organizer
      第62回トキシンシンポジウム
    • Place of Presentation
      エクシード合歓、賢島 (三重県、志摩市)
    • Year and Date
      2015-07-08
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Book] 天然物の化学II(科学のとびら64): 自然からの贈り物2018

    • Author(s)
      酒井隆一 (上村大輔編)
    • Total Pages
      192
    • Publisher
      東京化学同人
    • ISBN
      9784807915057
    • Related Report
      2018 Annual Research Report

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Published: 2015-04-16   Modified: 2020-03-30  

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