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Development of controlling technology for protein dissociation and aggregation using high pressure.

Research Project

Project/Area Number 21570163
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biophysics
Research InstitutionGifu University

Principal Investigator

KAMATARI Yujio  岐阜大学, 生命科学総合研究支援センター, 助教 (70342772)

Co-Investigator(Kenkyū-buntansha) MUTO Junji  科学警察研究所, 法科学第一部, 主任研究官 (80432186)
山口 圭一  岐阜大学, 人獣感染防御研究センター, 助教 (90432187)
Co-Investigator(Renkei-kenkyūsha) YAMAGUCHI Keiichi  岐阜大学, 連合創薬医療情報研究科, 特別研究員(PD)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2011: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords生物物理学 / フォールディング / 神経変性疾患 / プリオン病 / 凝集 / 圧力 / 巻き戻り / リゾチーム / 生物物理 / 脳神経疾患 / 能変性疾患 / 脳神経変性疾患
Research Abstract

Protein aggregation is one of the serious problems for human health and production of recombinant proteins. Purpose of this study is development of controlling technology for protein dissociation and aggregation using high pressure. In this study, we did following four topics. 1. We observed denaturation process of hen lysozyme using high pressure NMR spectroscopy, in which high pressure suppress protein aggregation. We succeed to observe low-lying excited states and unfolding intermediates at equilibrium condition(Kamatari et al., Biophys Chem. 156, 24-30, 2011). 2. We made a high-volume high pressure apparatus and did refolding experiments from inclusion bodies. 3. We made a high pressure apparatus for fluorescence spectroscopy and observed dissociation process of amyloid fibrils. 4. We used chemical compounds to suppress aggregation in addition to high pressure. We found several new anti-prion compounds(Hosokawa-Muto et al., Antimicrob. Agents Chemother., 53, 765-771, 2009). We optimized a anti-prion compound, GN8, and found higher efficiency compound than GN8(Kimura et al., Bioorg Med Chem Lett. 21, 1502-1507, 2011).

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (46 results)

All 2012 2011 2010 2009 Other

All Journal Article (15 results) (of which Peer Reviewed: 15 results) Presentation (26 results) Remarks (3 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Structure-based discovery of anti-influenza virus A compounds among medicines.2012

    • Author(s)
      Fukuoka M, Minakuchi M, Kawaguchi A, Nagata K, Kamatari Y, Kuwata K.
    • Journal Title

      Biochim. Biophys. Acta.

      Volume: 1820 Pages: 90-95

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Structure-based discovery of anti-influenza virus A compounds among medicines2012

    • Author(s)
      Fukuoka M., et al
    • Journal Title

      Biochim.Biophys.Acta.

      Volume: 1820 Issue: 2 Pages: 90-95

    • DOI

      10.1016/j.bbagen.2011.11.003

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 3,4-Dicaffeoylquinic Acid, a Major Constituent of Brazilian Propolis, Increases TRAIL Expression and Extends the Lifetimes of Mice Infected with the Influenza A Virus2012

    • Author(s)
      Takemura T, Urushisaki T, Fukuoka M, Hosokawa-Muto J, Hata T, Okuda Y, Hori S, Tazawa S, Araki Y, Kuwata K
    • Journal Title

      Evid.Based Complement.Alternat.Med.

      Volume: (in press) Pages: 1-7

    • DOI

      10.1155/2012/946867

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cavity hydration as a gateway to unfolding : An NMR study of hen lysozyme at high pressure and low temperature2011

    • Author(s)
      Kamatari, Y. O., Smith, L. J., Dobson, C. M., Akasaka, K.
    • Journal Title

      Biophys. Chem

      Volume: 156 Pages: 24-30

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis of GN8 derivatives and evaluation of their antiprion activity in TSE-infected cells.2011

    • Author(s)
      Kimura T, Hosokawa-Muto J, Kamatari YO, Kuwata K.
    • Journal Title

      Bioorg. Med. Chem. Lett.

      Volume: 21 Pages: 1502-1507

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Caffeoylquinic acids are major constituents with potent anti-influenza effects in brazilian green propolis water extract.2011

    • Author(s)
      Urushisaki T, Takemura T, Tazawa S, Fukuoka M, Hosokawa-Muto J, Araki Y, Kuwata K.
    • Journal Title

      Evid. Based Complement. Alternat. Med.

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] 3, 4-Dicaffeoylquinic Acid, a Major Constituent of Brazilian Propolis, Increases TRAIL Expression and Extends the Lifetimes of Mice Infected with the Influenza A Virus.2011

    • Author(s)
      Takemura T, Urushisaki T, Fukuoka M, Hosokawa-Muto J, Hata T, Okuda Y, Hori S, Tazawa S, Araki Y, Kuwata K.
    • Journal Title

      Evid. Based Complement. Alternat. Med.

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis of 9-substituted 2, 3, 4, 9-tetrahydro-1H-carbazole derivatives and evaluation of their anti-prion activity in TSE-infected cells2011

    • Author(s)
      Kimura T, Hosokawa-Muto J, Asami K, Murai T, Kuwata K.
    • Journal Title

      Eur. J. Med. Chem.

      Volume: 46 Pages: 5675-5679

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis of GN8 derivatives and evaluation of their antiprion activity in TSE-infected cells2011

    • Author(s)
      Kimura T, Hosokawa-Muto J, Kamatari YO, Kuwata K
    • Journal Title

      Bioorg.Med.Chem.Lett.

      Volume: 21 Issue: 5 Pages: 1502-1507

    • DOI

      10.1016/j.bmcl.2010.12.132

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Caffeoylquinic acids are major constituents with potent anti-influenza effects in brazilian green propolis water extract2011

    • Author(s)
      Urushisaki T, Takemura T, Tazawa S, Fukuoka M, Hosokawa-Muto J, Araki Y, Kuwata K
    • Journal Title

      Evid.Based Complement.Alternat.Med.

      Volume: (in press) Issue: 1

    • DOI

      10.1155/2011/254914

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis of 9-substituted 2,3,4,9-tetrahydro-1H-carbazole derivatives and evaluation of their anti-prion activity in TSE-infected cells2011

    • Author(s)
      Kimura T, Hosokawa-Muto J, Asami K, Murai T, Kuwata K
    • Journal Title

      Eur.J.Med.Chem.

      Volume: 46 Issue: 11 Pages: 5675-5679

    • DOI

      10.1016/j.ejmech.2011.08.039

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Respiratory and cardiovascular toxicity studies of a novel antiprion compound, GN8, in rats and dogs2011

    • Author(s)
      Hosokawa-Muto J, Kimura T, Kuwata K
    • Journal Title

      Drug.Chem.Toxicol.

      Volume: (in press) Issue: 3 Pages: 264-271

    • DOI

      10.3109/01480545.2011.598533

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cavity hydration as a gateway to unfolding : An NMR study of hen lysozyme at high pressure and low temperature2011

    • Author(s)
      Kamatari, Y.O., Smith, L.J., Dobson, C.M., Akasaka, K.
    • Journal Title

      Biophys.Chem.

      Volume: 156 Pages: 24-30

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Variety of antiprion compounds discovered through an in silico screen based on cellular-form prion protein structure : Correlation between antiprion activity and binding affinity.2009

    • Author(s)
      J. Hosokawa-Muto, Y. O. Kamatari, H. K. Nakamura, K. Kuwata
    • Journal Title

      Antimicrob. Agents Chemother.

      Volume: 53 Pages: 765-771

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Variety of antiprion compounds discovered through an in silico screen based on cellular-form prion protein structure : Correlation between antiprion activity and binding affinity.2009

    • Author(s)
      J.Hosokawa-Muto, Y.O.Kamatari, H.K.Nakamura, K.Kuwata
    • Journal Title

      Antimicrob.Agents Chemother. 53

      Pages: 765-771

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] 構造生物学・医学・論理的創薬の拠点構築を目指して2012

    • Author(s)
      鎌足雄司
    • Organizer
      第一回岐阜構造生物学・医学・論理的創薬研究会シンポジウム
    • Place of Presentation
      岐阜
    • Year and Date
      2012-03-23
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] Cavity hydration as a gateway to unfolding : An NMR study of hen lysozyme at high pressure and low temperature2011

    • Author(s)
      Y. O. Kamatari, L. J. Smith, C. M. Dobson, K. Akasaka
    • Organizer
      6th International Meeting on Biomolecules under Pressure
    • Place of Presentation
      滋賀
    • Year and Date
      2011-12-15
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] Low-lying excited state of prion protein directly linked to pathogenic conversion2011

    • Author(s)
      Y. O. Kamatari, K. Yamaguchi, & K. Kuwata
    • Organizer
      The International Symposium on Nuclear Magnetic Resonance 2011
    • Place of Presentation
      横浜
    • Year and Date
      2011-11-16
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] Cavity hydration as a gateway to unfolding : An NMR study of hen lysozyme at high pressure and low temperature2011

    • Author(s)
      Kamataria, Y. O., Akasaka, K.
    • Organizer
      第49回日本生物物理学会年会
    • Place of Presentation
      姫路
    • Year and Date
      2011-09-17
    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Presentation] Cavity hydration and the dynamics of a protein2011

    • Author(s)
      A. Maeno, R. Kitahara, Y. O. Kamatari, Sunilkumar P. N., K. Akasaka
    • Organizer
      第49回日本生物物理学会年会
    • Place of Presentation
      姫路
    • Year and Date
      2011-09-17
    • Related Report
      2011 Final Research Report
  • [Presentation] FK506 prolongs survival time of FK-1 infected mice2011

    • Author(s)
      T. Nakagaki, K. Satoh, Y. Kamatari, R. Atarashi, N. Nishida
    • Organizer
      International Union of Microbiological Sciences 2011 Congress
    • Place of Presentation
      札幌
    • Year and Date
      2011-09-15
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] Discovery of anti-influenza virus compounds from medicines on the market2011

    • Author(s)
      M. Fukuoka, M. Minakuchi, A. Kawaguchi, K. Nagata, Y. O Kamatari, K. Kuwata
    • Organizer
      International Union of Microbiological Sciences 2011 Congress
    • Place of Presentation
      札幌
    • Year and Date
      2011-09-15
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] プリオンタンパク質への結合様式による抗プリオン化合物の分類と作用機構の解明2010

    • Author(s)
      鎌足雄司,早野陽介,山口圭一,武藤(細川)淳二,桑田一夫
    • Organizer
      第49回NMR討論会
    • Place of Presentation
      東京
    • Year and Date
      2010-11-15
    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Presentation] Classification of anti-prion compounds based on the binding properties of prion proteins2010

    • Author(s)
      Kamatari, Y. O.
    • Organizer
      第48回日本生物物理学会年会
    • Place of Presentation
      仙台
    • Year and Date
      2010-09-21
    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Presentation] 蛍光共鳴エネルギー移動(FRET)による構造解析に向けたデュアルピンポイント蛍光標識プリオン蛋白質の合成2010

    • Author(s)
      武藤淳二
    • Organizer
      第149回日本獣医学会
    • Place of Presentation
      東京
    • Year and Date
      2010-03-26
    • Related Report
      2011 Final Research Report
  • [Presentation] プリオンタンパク質構造変換におけるホットスポットと抗プリオン化合物2009

    • Author(s)
      鎌足雄司
    • Organizer
      第2回先端創薬医療シンポジウム
    • Place of Presentation
      岐阜
    • Year and Date
      2009-12-19
    • Related Report
      2011 Final Research Report 2009 Annual Research Report
  • [Presentation] 無細胞蛋白質合成系を用いたデュアルピンポイント蛍光標識プリオン蛋白質の合成2009

    • Author(s)
      武藤淳二,山口圭一,鎌足雄司,桑田一夫
    • Organizer
      第4回無細胞生命科学研究会
    • Place of Presentation
      岐阜
    • Year and Date
      2009-11-16
    • Related Report
      2011 Final Research Report 2009 Annual Research Report
  • [Presentation] プリオンタンパク質構造変換におけるホットスポットと抗プリオン化合物2009

    • Author(s)
      鎌足雄司,早野陽介,木村力,武藤淳二,石倉孝一,山本典史,山口圭一,桑田一夫
    • Organizer
      第48回NMR討論会
    • Place of Presentation
      福岡
    • Year and Date
      2009-11-10
    • Related Report
      2011 Final Research Report 2009 Annual Research Report
  • [Presentation] 抗プリオン化合物GN8の類縁体合成および活性評価2009

    • Author(s)
      木村力,武藤淳二,鎌足雄司,桑田一夫
    • Organizer
      第40回中部化学関係学協会支部連合秋季大会
    • Place of Presentation
      岐阜
    • Year and Date
      2009-11-07
    • Related Report
      2011 Final Research Report 2009 Annual Research Report
  • [Presentation] プリオン病におけるタクロリムスの治療効果2009

    • Author(s)
      中垣岳大,佐藤克也,鎌足雄司,新竜一郎,石橋大輔,山口尚宏,西田教行
    • Organizer
      第57回日本ウイルス学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2009-10-26
    • Related Report
      2011 Final Research Report 2009 Annual Research Report
  • [Presentation] アンバーおよび4塩基コドンを用いたデュアルピンポイント蛍光標識プリオン蛋白質の合成2009

    • Author(s)
      武藤(細川)淳二,山口圭一,鎌足雄司,桑田一夫
    • Organizer
      第57回日本ウイルス学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2009-10-26
    • Related Report
      2011 Final Research Report 2009 Annual Research Report
  • [Presentation] Hot spot for pathogenic conversion of prion protein and anti-prion compounds2009

    • Author(s)
      鎌足雄司
    • Organizer
      Frontiers in Nanoscience and Technology-Multi-dimension Seminar
    • Place of Presentation
      石川
    • Year and Date
      2009-10-14
    • Related Report
      2011 Final Research Report
  • [Presentation] Hot spot for pathogenic conversion of prion protein and anti-prion compunds2009

    • Author(s)
      鎌足雄司
    • Organizer
      Frontiers in Nanoscience and Technology -Multi- dimension Seminar
    • Place of Presentation
      石川
    • Year and Date
      2009-10-14
    • Related Report
      2009 Annual Research Report
  • [Presentation] Synthesis of Isotope Labeled Anti-Prion Compound GN8 Derivative and Evaluation of Its Blood-Brain Barrier Permeability Using Positron Emission Tomography2009

    • Author(s)
      T.Kimura、J.Muto、Y.O.Kamatari、K.Kuwata
    • Organizer
      2009 World Molecular Imaging Congress
    • Place of Presentation
      Montreal, Canada
    • Year and Date
      2009-09-24
    • Related Report
      2009 Annual Research Report
  • [Presentation] Synthesis of Isotope Labeled Anti-Prion Compound GN8 Derivative and Evaluation of Its Blood-Brain Barrier Permeability Using Positron Emission Tomography2009

    • Author(s)
      T. Kimura、J. Muto、Y. O. Kamatari、K. Kuwata
    • Organizer
      Montreal
    • Place of Presentation
      Canada
    • Year and Date
      2009-09-23
    • Related Report
      2011 Final Research Report
  • [Presentation] NMRでタンパク質の構造・揺らぎ・相互作用を見る2009

    • Author(s)
      鎌足雄司,桑田一夫
    • Organizer
      第16回岐阜シンポジウム
    • Place of Presentation
      岐阜
    • Year and Date
      2009-07-08
    • Related Report
      2011 Final Research Report 2009 Annual Research Report
  • [Presentation] 論理的創薬による抗ウイルス薬の開発2009

    • Author(s)
      福岡万佑子,中村寛則,鎌足雄司,桑田一夫
    • Organizer
      第16回岐阜シンポジウム
    • Place of Presentation
      岐阜
    • Year and Date
      2009-07-08
    • Related Report
      2011 Final Research Report 2009 Annual Research Report
  • [Presentation] Identification of a variety of anti-prion compounds that acts as chemical chaperons2009

    • Author(s)
      Y. O. Kamatari, J. Hosokawa-Muto, H. K. Nakamura, Y. Hayano, K. Kuwata
    • Organizer
      VIII European Symposium of The Protein Society
    • Place of Presentation
      Zurich, Switzerland
    • Year and Date
      2009-06-17
    • Related Report
      2011 Final Research Report 2009 Annual Research Report
  • [Presentation] New evaluation scheme for anti-prion compounds using ensemble of docking models2009

    • Author(s)
      H. K. Nakamura, J. Hosokawa-Muto, Y. O. Kamatari, K. Kuwata
    • Organizer
      VIII European Symposium of The Protein Society
    • Place of Presentation
      Zurich, Switzerland
    • Year and Date
      2009-06-17
    • Related Report
      2011 Final Research Report 2009 Annual Research Report
  • [Presentation] Development of double-fluorescent-labeled prion protein system for FRET analysis2009

    • Author(s)
      J. Muto, K.-I. Yamaguchi, Y. O. Kamatari, K. Kuwata
    • Organizer
      VIII European Symposium of The Protein Society
    • Place of Presentation
      Zurich, Switzerland
    • Year and Date
      2009-06-16
    • Related Report
      2011 Final Research Report 2009 Annual Research Report
  • [Presentation] 作用機構による抗プリオン化合物の分類2009

    • Author(s)
      鎌足雄司
    • Organizer
      第2回長崎プリオン研究会
    • Place of Presentation
      長崎
    • Year and Date
      2009-04-17
    • Related Report
      2011 Final Research Report 2009 Annual Research Report
  • [Remarks]

    • URL

      http://www1.gifu-u.ac.jp/~kamatari/publication.html

    • Related Report
      2011 Final Research Report
  • [Remarks]

    • URL

      http://www1.gifu-u.ac.jp/~kamatari/publication.html

    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://www1.gifu-u.ac.jp/~kamatari/publication.html

    • Related Report
      2010 Annual Research Report
  • [Patent(Industrial Property Rights)] プリオンタンパク質構造変換抑制剤及びその利用2009

    • Inventor(s)
      桑田一夫、木村力、武藤淳二
    • Industrial Property Rights Holder
      岐阜大学
    • Industrial Property Number
      2009-118076
    • Filing Date
      2009-05-14
    • Related Report
      2011 Final Research Report
  • [Patent(Industrial Property Rights)] アイソトープ標識化合物及びアイソトープ標識化合物前駆体2009

    • Inventor(s)
      桑田一夫、木村力、武藤淳二、古山浩子、鈴木正昭、渡辺恭良、土居久志、佐古健生
    • Industrial Property Rights Holder
      理化学研究所、岐阜大学
    • Industrial Property Number
      2009-218247
    • Acquisition Date
      2009-09-21
    • Related Report
      2011 Final Research Report

URL: 

Published: 2009-04-01   Modified: 2016-04-21  

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