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2011 Fiscal Year Final Research Report

Research on pathological mechanism of amyloid beta peptide and application to the aggregation inhibitor

Research Project

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Project/Area Number 22790118
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Drug development chemistry
Research InstitutionThe University of Tokyo (2011)
Kyoto Pharmaceutical University (2010)

Principal Investigator

YOUHEI Sohma  東京大学, 大学院・薬学系研究科, 特任研究員 (10565518)

Project Period (FY) 2010 – 2011
Keywordsアミロイド / アルツハイマー病 / イソペプチド / ペプチド / 凝集 / 阻害剤
Research Abstract

Studies with the O-acyl isopeptides of A〓 mutants and pyroGlu-A〓 enabled us to identify new functions of amyloid beta peptides. In addition, the O-acyl isopeptide of A〓1〓42 with an ester bond at the Gly25〓Ser26 moiety had a capability of inhibiting fibril formation of A〓1〓42 at equimolar ratio.

  • Research Products

    (21 results)

All 2013 2012 2011 2010

All Journal Article (11 results) (of which Peer Reviewed: 11 results) Presentation (8 results) Book (2 results)

  • [Journal Article] Comparative properties of A〓1〓42, A〓11〓42, and [Pyr11]A〓11〓42 generated from O-acyl isopeptides2013

    • Author(s)
      Youhei Sohma, Moe Yamasaki, Hiroyuki Kawashima, Atsuhiko Taniguchi, Masayuki Yamashita, Kenichi Akaji, Hidehito Mukai, Yoshiaki Kiso
    • Journal Title

      Bioorg. Med. Chem. Lett.

      Volume: 23 Pages: 1326-1329

    • URL

      http://dx.doi.org/10.1016/j.bmcl.2012.12.082

    • Peer Reviewed
  • [Journal Article] Synthesis of O-acyl isopeptides2013

    • Author(s)
      Youhei Sohma, Yoshiaki Kiso
    • Journal Title

      Chem. Rec.

      Volume: 13 Pages: 218-223

    • DOI

      DOI:10.1002/tcr.201200023

    • Peer Reviewed
  • [Journal Article] Through the looking glass-a new world of proteins enabled by chemical synthesis2012

    • Author(s)
      Stephen Kent, Youhei Sohma, Suhuai Liu, Duhee Bang, Brad Pentelute and Kalyaneswar Mandal
    • Journal Title

      J. Peptide Science

      Volume: 18 Pages: 428-436

    • DOI

      DOI:10.1002/psc.2421

    • Peer Reviewed
  • [Journal Article] S-Acyl isopeptide method: use of allyl-type protective group for improved preparation of thioester-containing S-acyl isopeptides by Fmoc-based SPPS.2011

    • Author(s)
      Taku Yoshiya, Yuka Hasegawa, Wakana Kawamura, Hiroyuki Kawashima, Youhei Sohma, Tooru Kimura, Yoshiaki Kiso
    • Journal Title

      Biopolymers

      Volume: 96 Pages: 228-239

    • DOI

      DOI 10.1002/bip.21410

    • Peer Reviewed
  • [Journal Article] Synthesis of the sphingolipid activator protein, saposin C, using an azido-protected O-acyl isopeptide as an aggregation-disrupting element.2011

    • Author(s)
      Hironobu Hojo, Hidekazu Katayama, Chiharu Tano, Yuko Nakahara, Azusa Yoneshige, Junko Matsuda, Youhei Sohma, Yoshiaki Kiso, Yoshiaki Nakahara
    • Journal Title

      Tetrahedron Lett.

      Volume: 52 Pages: 635-639

    • DOI

      DOI:10.1016/j.tetlet.2010.11.154

    • Peer Reviewed
  • [Journal Article] 'Click peptide'using production of monomer A〓 from the O-acyl isopeptide:Application to assay system of aggregation inhibitorsand cellular cytotoxicity.2011

    • Author(s)
      Youhei Sohma, Yuta Hirayama, Atsuhiko Taniguchi, Hidehito Mukai, Yoshiaki Kiso
    • Journal Title

      Bioorg. Med. Chem.

      Volume: 19 Pages: 1729-1733

    • DOI

      DOI:10.1016/j.bmc.2011.01.021

    • Peer Reviewed
  • [Journal Article] Click peptide"concept:O-acyl isopeptide of islet amyloid polypeptide as a non-aggregative precursor molecule2011

    • Author(s)
      Taku Yoshiya, Ayano Higa, Naoko Abe, Fukue Fukao, Tomomi Kuruma, Yuki Toda, Youhei Sohma, Yoshiaki Kiso
    • Journal Title

      ChemBioChem

      Volume: 12 Pages: 1216-1222

    • DOI

      DOI:10.1002/cbic.201100025

    • Peer Reviewed
  • [Journal Article] Self-assembly pathways of E22delta-type amyloid〓 peptide mutants generated from non-aggregative O-acyl isopeptide precursors2011

    • Author(s)
      Youhei Sohma, Hui Wang, Atsuhiko Taniguchi, Yuta Hirayama, Taeko Kakizawa, Moe Yamasaki, Hidehito Mukai, Yoshiaki Kiso
    • Journal Title

      Bioorg. Med. Chem.

      Volume: 19 Pages: 3787-3792

    • DOI

      DOI:10.1016/j.bmc.2011.04.056

    • Peer Reviewed
  • [Journal Article] Structure-guided design and synthesis of P1〓 position1-phenylcycloalkylamine-derived pentapeptidic BACE1 inhibitors2011

    • Author(s)
      Harichandra D. Tagad, Yoshio Hamada, Jeffrey-Tri Nguyen, Koushi Hidaka, Takashi Hamada, Youhei Sohma, Tooru Kimura, Yoshiaki Kiso
    • Journal Title

      Bioorg. Med. Chem.

      Volume: 19 Pages: 5238-5246

    • DOI

      DOI:10.1016/j.bmc.2011.07.002

    • Peer Reviewed
  • [Journal Article] Synthesis of an O-acyl isopeptide by using native chemical ligation to efficiently construct a hydrophobic polypeptide2011

    • Author(s)
      Youhei Sohma, Hitomi Kitamura, Hiroyuki Kawashima, Hironobu Hojo, Masayuki Yamashita, Kenichi Akaji, Yoshiaki Kiso
    • Journal Title

      Tetrahedron Lett.

      Volume: 52 Pages: 7146-7148

    • DOI

      DOI:10.1016/j.tetlet.2011.10.116

    • Peer Reviewed
  • [Journal Article] Epimerization-free synthesis of cyclic peptide by use of the O-acyl isopeptide method.2010

    • Author(s)
      Taku Yoshiya, Hiroyuki Kawashima, Yuka Hasegawa, Kazuhiro Okamoto, Tooru Kimura, Youhei Sohma, Yoshiaki Kiso
    • Journal Title

      J. Peptide Sci.

      Volume: 16 Pages: 437-442

    • DOI

      DOI 10.1002/psc.1261

    • Peer Reviewed
  • [Presentation] ネイティブケミカルライゲーション法を利用したO-アシルイソペプチドの合成2011

    • Author(s)
      相馬洋平、北村仁美、川島浩之、北條裕信、赤路健一、木曽良明
    • Organizer
      第61回日本薬学会近畿支部総会・大会
    • Place of Presentation
      神戸
    • Year and Date
      2011-10-22
  • [Presentation] エステル含有ペプチドを基盤とした生物有機化学研究2011

    • Author(s)
      相馬洋平
    • Organizer
      第46回天然物化学談話会
    • Place of Presentation
      熱川
    • Year and Date
      2011-07-08
  • [Presentation] アミロイドベータペプチドおよびアミリンの凝集機構解明を目指したO-アシルイソペプチ ドの利用2011

    • Author(s)
      相馬洋平Hui Wang山崎 萌,平山雄 太,谷口敦彦,川島浩之,比嘉彩乃,吉矢 拓,向井秀仁,木曽良明
    • Organizer
      第9回次世代を担う有機化学シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2011-05-12
  • [Presentation] Use of ester-containing peptides for identifying the functions of human insulin and amyloid peptide2010

    • Author(s)
      Youhei Sohma
    • Organizer
      大阪大学蛋白質研究所セミナーNew Trend of Peptide Science in Asia and Oceania
    • Place of Presentation
      大阪
    • Year and Date
      2010-12-10
  • [Presentation] Use of O-acyl isopeptides to identify new functions of amyloid beta peptides2010

    • Author(s)
      Youhei Sohma, Atsuhiko Taniguchi, Yuta Hirayama, Hui Wang, Moe Yamazaki, Hidehito Mukai, Yoshiaki Kiso
    • Organizer
      5th International Peptide Symposium
    • Place of Presentation
      Kyoto
    • Year and Date
      2010-12-04
  • [Presentation] Use of O-acyl isopeptides to identify new functions of amyloid beta peptides2010

    • Author(s)
      Youhei Sohma, Atsuhiko Taniguchi, Yuta Hirayama, Hui Wang, Moe Yamazaki, Hidehito Mukai, Yoshiaki Kiso
    • Organizer
      31st European Peptides Symposium
    • Place of Presentation
      Copenhagen,Denmark
    • Year and Date
      2010-09-05
  • [Presentation] アミロイドβペプチドおよびインスリンの機能解明を目指したエステル含有ペプ チドの利用2010

    • Author(s)
      相馬洋平、谷口敦彦、向井 秀仁、Stephen B. H. Kent、木曽良明
    • Organizer
      日本ケミカルバイオロジー学会第5回年会
    • Place of Presentation
      横浜
    • Year and Date
      2010-05-18
  • [Presentation] エルテルまたはチオエステルを含むペプチド合成法開発とその生物研究への応用2010

    • Author(s)
      相馬洋平,Stephen B. H. Kent,木曽良明
    • Organizer
      第8回次世代を担う有機化学シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2010-05-13
  • [Book] ペプチド医薬の最前線2012

    • Author(s)
      相馬洋平
    • Publisher
      シーエムシー出版
  • [Book] 最新ペプチド合成技術とその創薬研究への応用2011

    • Author(s)
      相馬洋平
    • Publisher
      遺伝子医学MOOK21号, メディカルドウ

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Published: 2014-08-29  

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