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Investigation of interfaces on protein among aggregate on living cell

Research Project

Project/Area Number 15K01804
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Biomolecular chemistry
Research InstitutionTohoku University

Principal Investigator

Teruya Kenta  東北大学, 医学系研究科, 准教授 (30372288)

Project Period (FY) 2015-10-21 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywordsプリオン / クロスリンク / 光反応 / 増感剤 / 異常型プリオン蛋白質 / 多量体
Outline of Final Research Achievements

Molecular pathology of prion diseases is characterized by abnormal prion protein (PrPSc), which involves both structural changes at the molecular level and aggregate formation. Understanding of the interface among PrPSc in the aggregate is a core subject in prion. In general, a bis-functionalized crosslinker is used to analyze. Since the normal and abnormal PrP are identical in the denatured state, it is principally difficult to adapt for access the molecule in the fibril. Thus, methods have been required to mark on a protein molecule in the fibril before denaturation.
I found a method that can solve the lemma by a photo-reaction, furthermore, beneficial sensitizers. As results, I established a crosslinking method that is effective in contaminated systems and selective for PrPSc. Also, the method is compatible with purification and a biochemical method for discrimination of PrPSc from normal one. Finally, an anti-body panel indicated the a specific region of PrPSc confer the interface.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (33 results)

All 2017 2016 2015 Other

All Journal Article (14 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 14 results,  Open Access: 6 results,  Acknowledgement Compliant: 2 results) Presentation (16 results) (of which Int'l Joint Research: 8 results,  Invited: 3 results) Remarks (2 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Pyrene conjugation and spectroscopic analysis of hydroxypropyl methylcellulose compounds successfully demonstrated a local dielectric difference associated with in vivo anti-prion activity.2017

    • Author(s)
      Teruya K, Oguma A, Nishizawa K, Kamitakahara H, Doh-ura K.
    • Journal Title

      PLoS One.

      Volume: 12(9) Issue: 9 Pages: e0185357-e0185357

    • DOI

      10.1371/journal.pone.0185357

    • NAID

      120006878530

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Synthesis and evaluation of phenylisoserine derivatives for the SARS-CoV 3CL protease inhibitor2017

    • Author(s)
      Konno Hiroyuki、Onuma Takumi、Nitanai Ikumi、Wakabayashi Masaki、Yano Shigekazu、Teruya Kenta、Akaji Kenichi
    • Journal Title

      Bioorg. Med. Chem. Lett.

      Volume: 27 Issue: 12 Pages: 2746-2751

    • DOI

      10.1016/j.bmcl.2017.04.056

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Melanin or melanin-like substance interacts with the N-terminal portion of prion protein and inhibits abnormal prion protein formation in prion-infected cells.2017

    • Author(s)
      Taichi Hamanaka, Keiko Nishizawa, Yuji Sakasegawa, Ayumi Oguma, Kenta Teruya, Hiroshi Kurahashi, Hideyuki Hara, Suehiro Sakaguchi, Katsumi Doh-ura
    • Journal Title

      Journal of Virology

      Volume: 印刷中 Issue: 6

    • DOI

      10.1128/jvi.01862-16

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Insights from Therapeutic Studies for PrP Prion Disease.2017

    • Author(s)
      Teruya K, Doh-ura K.
    • Journal Title

      Cold Spring Harb Perspect Med.

      Volume: 7(3) Issue: 3 Pages: a024430-a024430

    • DOI

      10.1101/cshperspect.a024430

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] A Single Subcutaneous Injection of Cellulose Ethers Administered Long before Infection Confers Sustained Protection against Prion Diseases in Rodents.2016

    • Author(s)
      Teruya K, Oguma A, Nishizawa K, Kawata M, Sakasegawa Y, Kamitakahara H, Doh-ura K.
    • Journal Title

      PLoS Pathog.

      Volume: 12(12) Issue: 12 Pages: e1006045-e1006045

    • DOI

      10.1371/journal.ppat.1006045

    • NAID

      120005980891

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Structure-activity analysis and antiprion mechanism of isoprenoid compounds2015

    • Author(s)
      Hamanaka T, Nishizawa K, Sakasegawa Y, Teruya K, Doh-ura K.
    • Journal Title

      Virology

      Volume: 486 Pages: 63-70

    • DOI

      10.1016/j.virol.2015.09.002

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Anti-prion activity found in beetle grub hemolymph of Trypoxylus dichotomus septentrionalis2015

    • Author(s)
      Hamanaka T, Nishizawa K, Sakasegawa Y, Kurahashi H, Oguma A, Teruya K, Doh-ura K.
    • Journal Title

      Biochemistry and Biophysics Reports

      Volume: 3 Pages: 332-337

    • DOI

      10.1016/j.bbrep.2015.07.009

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Evaluation of transition-state mimics in a superior BACE1 cleavage sequence as peptide-mimetic BACE1 inhibitors2015

    • Author(s)
      Hattori Y, Kobayashi K, Deguchi A, Nohara Y, Akiyama T, Teruya K, Sanjoh A, Nakagawa A, Yamashita E, Akaji K
    • Journal Title

      Bioorganic and Medicinal Chemistry

      Volume: 23 Issue: 17 Pages: 5626-5640

    • DOI

      10.1016/j.bmc.2015.07.023

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] The influence of PRNP polymorphisms on human prion disease susceptibility: an update2015

    • Author(s)
      Kobayashi A, Teruya K, Matsuura Y, Shirai T, Nakamura Y, Yamada M, Mizusawa H, Mohri S, Kitamoto T.
    • Journal Title

      Acta Neuropathologica

      Volume: 130 Issue: 2 Pages: 159-170

    • DOI

      10.1007/s00401-015-1447-7

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Secretin Receptor Involvement in Prion-Infected Cells and Animals2015

    • Author(s)
      Kimura T, Nishizawa K, Oguma A., Nishimura Y, Sakasegawa Y, Teruya K, Nishijima I, Doh-ura K.
    • Journal Title

      FEBS Letters

      Volume: 589 Issue: 15 Pages: 2011-2018

    • DOI

      10.1016/j.febslet.2015.05.039

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Heparinase I-specific disaccharide unit of heparin is a key structure but insufficient for exerting anti-prion activity in prion-infected cells2015

    • Author(s)
      Teruya K, Wakao M, Sato M, Hamanaka T, Nishizawa K, Funayama Y, Sakasegawa Y, Suda Y, Doh-ura K.
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 460 Issue: 4 Pages: 989-995

    • DOI

      10.1016/j.bbrc.2015.03.139

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Divergent Synthesis of 2,6-Disubstituted Piperidine Alkaloid, (+)-Spectaline by Palladium-Catalyzed Cyclization2015

    • Author(s)
      Katsuyama M, Furuta M, Kobayashi K, Teruya K, Makabe H, Akaji K, Hattori Y.
    • Journal Title

      HETEROCYCLES

      Volume: 91 Issue: 5 Pages: 959-969

    • DOI

      10.3987/com-15-13172

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Synthesis of a pyrrolidine analog of a tetrahydrofuran containing acetogenin, cis-solamin2015

    • Author(s)
      Ohnishi K, Sakurai H, Katsuyama M, Kobayashi K, Makabe H, Teruya K, Akaji K, Hattori Y.
    • Journal Title

      HETEROCYCLES

      Volume: 91 Issue: 3 Pages: 573-582

    • DOI

      10.3987/com-14-13163

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Fused-ring structure of decahydroisoquinolin as a novel scaffold for SARS 3CL protease inhibitors2015

    • Author(s)
      Shimamoto Y, Hattori Y, Kobayashi K, Teruya K, Sanjho A, Nakagawa A, Yamashita E, Akaji K.
    • Journal Title

      Bioorganic and Medicinal Chemistry

      Volume: 23 Issue: 4 Pages: 876-890

    • DOI

      10.1016/j.bmc.2014.12.028

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Presentation] デカヒドロイソキノリン骨格を基盤とする新規縮環構造型SARS 3CL protease阻害の設計と合成2017

    • Author(s)
      大西康司、嶋本康広、小林数也、服部恭尚、照屋健太、赤路健一
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台市(仙台国際センター )
    • Year and Date
      2017-03-24
    • Related Report
      2016 Research-status Report
  • [Presentation] Current Therapeutic Development for Prion Disease2017

    • Author(s)
      照屋健太
    • Organizer
      第25回山形分子生物学セミナー
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Cellulose ether compounds exert protection to prion infection; a biological parameter related to the effectiveness of compounds2017

    • Author(s)
      Katsumi Doh-ura, Kenta Teruya, Keiko Nishizawa, Ayumi Oguma, Yuji Sakasegawa, Hiroshi Kamitakahara
    • Organizer
      Asia Pacific Prion Symposium 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Anti-prion activities of cellulose ether compounds in prion-infected cells are consistent with long-lasting anti-prion activities in vivo.2017

    • Author(s)
      Keiko Nishizawa, Kenta Teruya, Ayumi Oguma, Yuji Sakasegawa, Katsumi Doh-ura
    • Organizer
      Asia Pacific Prion Symposium 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Pyrene index of hydroxypropyl methylcellulose compounds correlates with the in vivo long-lasting anti-prion activity2017

    • Author(s)
      Kenta Teruya, Ayumi Oguma, Keiko Nishizawa, Hiroshi Kamitakahara, Katsumi Doh-ura
    • Organizer
      Asia Pacific Prion Symposium 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Current Therapeutic Development for Prion Disease2017

    • Author(s)
      Kenta Teruya
    • Organizer
      第60回神経化学大会サテライトシンポジウム 「Protein Misfolding Disease and Therapy 2017」
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] ウイルス感染症の新規治療薬開発を目指した標的蛋白質阻害剤複合体の構造生物学研究2017

    • Author(s)
      三城明、照屋健太、赤路健一
    • Organizer
      第6回名大シンクロトロン光研究センターシンポジウム
    • Place of Presentation
      名古屋市(名古屋大学 野依記念学術交流館)
    • Related Report
      2016 Research-status Report
  • [Presentation] プリオン病治療法開発の現状:わが国と海外2017

    • Author(s)
      照屋健太
    • Organizer
      2016年度 プリオン病のサーベイランスと対策に関する全国担当者会議
    • Place of Presentation
      東京都千代田区(アルカディア市ヶ谷)
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] SELECTIVE PRPSC CROSSLINKING REACTION DETECTED BY WESTERN BLOTTING2016

    • Author(s)
      Kenta Teruya, Katsumi Doh-ura
    • Organizer
      第53回ペプチド討論会
    • Place of Presentation
      京都市(京都テルサ)
    • Year and Date
      2016-10-26
    • Related Report
      2016 Research-status Report
  • [Presentation] A case study of development of inhibitor to a disease related enzyme based on structural and chemometrical analysis2016

    • Author(s)
      Kenta Teruya, Yasunao Hattori, Akira Sanjoh, Eiki Yamashita, Atsushi Nakagawa, Kenichi Akaji
    • Organizer
      42nd Naito Conference “In the Vanguard of Structural Biology: Revolutionizing Life Sciences”
    • Place of Presentation
      札幌市(シャトレーゼ ガトーキングダム サッポロ)
    • Year and Date
      2016-10-04
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] デカヒドロイソキノリン骨格を基盤とする新規縮環型SARS 3CLプロテアーゼの設計・合成と複合体構造解析2016

    • Author(s)
      大西康司、服部恭尚、小林数也、嶋本康広、照屋健太、三城明、赤路健一
    • Organizer
      第46回 複素環化学討論会
    • Place of Presentation
      金沢市(金沢歌劇座)
    • Year and Date
      2016-09-26
    • Related Report
      2016 Research-status Report
  • [Presentation] Dimer sized PrPSc formation detected by western blotting.2016

    • Author(s)
      Kenta Teruya, Katsumi Doh-ura
    • Organizer
      PRION 2016 conjugation with Asian Pacific Prion Symposium 2016
    • Place of Presentation
      東京都千代田区(一ツ橋ホール)
    • Year and Date
      2016-05-10
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Effects of cell growth suppression treatments on PrPSc accumulation in prion-infected cells; Paradoxical phenomena observed in butyric acid treatment2016

    • Author(s)
      Takako Hiyoshi, Yuji Sakasegawa, Keiko Nishizawa, Kenta Teruya, Katsumi Doh-ura
    • Organizer
      PRION 2016 conjugation with Asian Pacific Prion Symposium 2016
    • Place of Presentation
      東京都千代田区(一ツ橋ホール)
    • Year and Date
      2016-05-10
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] SARS 3CL プロテアーゼ阻害剤を目指したイソセリン誘導体の合成と評価2016

    • Author(s)
      今野博行、若林雅貴、似内郁美、照屋健太、赤路健一
    • Organizer
      農芸化学会東北支部会
    • Place of Presentation
      山形市(山形大学農学部(鶴岡キャンパス))
    • Related Report
      2016 Research-status Report
  • [Presentation] Evaluation of Hydroxymethylcarbonyl and Hydroxyethylamine Isosteres in a Superior BACE 1 Cheavage Sequence for BACE1 Inhibitors.2015

    • Author(s)
      Kazuya Kobayashi, Yasunao Hattori, Ayaka Deguchi, Yukie Nohara, Tomomi Akiyama, Kenta Teruya, Akira Sanjoh, Atsushi Nakagawa, Eiki Yamashita, Kenichi Akaji
    • Organizer
      7th International Peptide Symposium
    • Place of Presentation
      Republic of Singapore, Singapore
    • Year and Date
      2015-12-09
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] A CHEMOMETRICAL ANALYSIS OF STRUCTURES OF SARS 3CL PROTEASE COMPLEXED WITH INHIBITOR2015

    • Author(s)
      照屋健太、服部恭尚、嶋本康広、小林数也、三城明、山下栄樹、中川敦史、赤路健一
    • Organizer
      第52回ペプチド討論会
    • Place of Presentation
      神奈川県平塚市, 平塚中央公民館
    • Year and Date
      2015-11-16
    • Related Report
      2015 Research-status Report
  • [Remarks] 東北大学大学院 医学系研究科 神経化学分野

    • URL

      http://www.neurochemistry.med.tohoku.ac.jp/NC/NC_teruya.html

    • Related Report
      2017 Annual Research Report
  • [Remarks] 東北大学大学院 医学系研究科 神経化学分野

    • URL

      http://www.neurochemistry.med.tohoku.ac.jp/

    • Related Report
      2016 Research-status Report 2015 Research-status Report
  • [Patent(Industrial Property Rights)] コンフォメーション病医薬組成物及びその製造方法2016

    • Inventor(s)
      堂浦克美、照屋健太、西澤桂子、小熊歩
    • Industrial Property Rights Holder
      国立大学法人東北大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2016-05-09
    • Related Report
      2016 Research-status Report

URL: 

Published: 2015-10-21   Modified: 2019-03-29  

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