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

• Project/Area Number: 22790118
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Drug development chemistry
• Research Institution: The 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
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2010: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• 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 / クリックペプチド

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

• [Journal Article] Comparative properties of A〓1〓42, A〓11〓42, and [Pyr11]A〓11〓42 generated from O-acyl isopeptides (2013)
  • 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 Isopeptides. (2013)
  • Author(s): Youhei Sohma
  • Journal Title: Chemical Record Volume: 13 Issue: 2 Pages: 218-223
  • DOI: 10.1002/tcr.201200023
  • Peer Reviewed
• [Journal Article] Comparative Properties of AB1-42, AB11-42 and [Pyr11]AB11-42 Generated from O-Acyl Isopeptides (2013)
  • Author(s): Youhei Sohma
  • Journal Title: Bioorganic & Medicinal Chemistry Letters Volume: 23 Pages: 1326-1329
  • Peer Reviewed
• [Journal Article] Through the looking glass-a new world of proteins enabled by chemical synthesis (2012)
  • Author(s): Stephen Kent, Youhei Sohma, Suhuai Liu, Duhee Bang, Brad Pentelute and Kalyaneswar Mandal
  • Journal Title: J. Peptide Science Volume: 18 Issue: 7 Pages: 428-436
  • 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 Issue: 2 Pages: 228-239
  • 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 Issue: 5 Pages: 635
  • DOI: 10.1016/j.tetlet.2010.11.154
  • URL: https://pure.teikyo.jp/en/publications/e1527374-53f5-449f-b5c0-db6360985787
  • Peer Reviewed
• [Journal Article] 'Click peptide' using production of monomer Ab from the O-acyl isopeptide: Application to assay system of aggregation inhibitors and cellular cytotoxicity. (2011)
  • Author(s): Youhei Sohma, Yuta Hirayama, AtsuhikoTaniguchi, Hidehito Mukai, Yoshiaki Kiso
  • Journal Title: Bioorg. Med. Chem. Volume: 19 Issue: 5 Pages: 1729-1733
  • DOI: 10.1016/j.bmc.2011.01.021
  • Peer Reviewed
• [Journal Article] "Click Peptide" Concept: O-Acyl Isopeptide of Islet Amyloid Poly- peptide As a non-aggregative precursor molecule. (2011)
  • Author(s): Taku Yoshiya, Ayano Higa, Naoko Abe, Fukue Fukao, Tomomi Kuruma, Youhei Sohma, Yoshiaki Kiso
  • Journal Title: ChemBioChem. Volume: 12(8) Issue: 8 Pages: 1216-1222
  • DOI: 10.1002/cbic.201100025
  • Peer Reviewed
• [Journal Article] The E22SS-type mutant of amyloid SS peptide (ASS) adopts distinct selfassembly mechanisms from wild- type ASS. (2011)
  • Author(s): Youhei Sohma, Hui Wang, Atsuhiko Taniguchi, Yuta Hirayama, Taeko Kakizawa, Hidehito Mukai, Yoshiaki Kiso
  • Journal Title: Bioorg. Med. Chem. Volume: 19 Issue: 12 Pages: 3787-3792
  • DOI: 10.1016/j.bmc.2011.04.056
  • Peer Reviewed
• [Journal Article] Structure-guided design and synthesis of P1' position 1-phenylcycloalkyl-amine-derived pentapeptidic BACE1 inhibitors. (2011)
  • 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 Issue: 17 Pages: 5238-5246
  • 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 polypeptide. (2011)
  • Author(s): Youhei Sohma, Hitomi Kitamura, Hiroyuki Kawashima, Hironobu Hojo, Masayuki Yamashita, Kenichi Akaji, Yoshiaki Kiso
  • Journal Title: Tetrahedron Letters Volume: 52(52) Issue: 52 Pages: 7146-7148
  • DOI: 10.1016/j.tetlet.2011.10.116
  • NAID: 10030204148
  • Peer Reviewed
• [Journal Article] 'Click peptide'using production of monomer Ab from the O-acyl isopeptide : Application to assay system of aggregation inhibitors and cellular cytotoxicity (2011)
  • Author(s): Youhei Sohma
  • Journal Title: Bioorg.Med.Chem. Volume: 19 Pages: 1729-1733
  • Peer Reviewed
• [Journal Article] Racemization- 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 Science. Volume: 16(8) Issue: 8 Pages: 437-442
  • DOI: 10.1002/psc.1261
  • Peer Reviewed
• [Journal Article] Epimerization-free synthesis of cyclic peptide by use of the O-acyl isopeptide method. (2010)
  • Author(s): Taku Yoshiya
  • Journal Title: J.Peptide Sci. Volume: 16 Pages: 437-442
  • 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. (2010)
  • Author(s): Taku Yoshiya
  • Journal Title: Biopolymers Volume: 96 Pages: 228-239
  • 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 peptide (2010)
  • 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 peptides (2010)
  • 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 peptides (2010)
  • 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
• [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
  • 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
• [Presentation] Use of ester-containing peptides toward understanding the functions of amyloid beta peptide and human insulin. (2010)
  • Author(s): Youhei Sohma
  • Organizer: 31st European Peptides Symposium
  • Place of Presentation: Copenhagen, Denmark
• [Presentation] Use of O-Acyl isopeptides to identify new functions of amyloid beta peptides. (2010)
  • Author(s): Youhei Sohma
  • Organizer: 5th International Peptide Symposium
  • Place of Presentation: Kyoto
• [Presentation] Use of ester-containing peptides for identifying the functions of human insulin and amyloid peptide. (2010)
  • 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
• [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