Development of new anchor molecule to fix biologically active molecules on cell surface

• Project/Area Number: 15K12758
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Chemical biology
• Research Institution: Osaka City University
• Principal Investigator: Shinada Tetsuro 大阪市立大学, 大学院理学研究科, 教授 (30271513)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 細胞膜 / 情報伝達 / 錨分子 / ドリコール / ポリイソプレノイド / 立体化学 / トランス型 / イソプレノイド / 幾何異性 / 生体膜 / 相互作用 / テルペノイド / 脂質二重膜 / 有機合成

Outline of Final Research Achievements

To analyze biological events and signal transduction on cell surface, we envisioned a new anchor molecule to fix biologically active molecules on the cell surface. As a new anchor, we designed a dolichol analog with all trans olefins (C100). The designed molecule is not available from nature and has not been synthesized yet. Therefore, we attempted the first synthesis of the C100 anchor. After extensive studies, the target molecule was successfully synthesized by coupling of C45 and C55 units that was prepared by linkage of three C15 units and a C10 unit. Phosphorylation of the C100 anchor was attempted.

Research Products

• [Journal Article] Crystal structure and functional analysis of large-terpene synthase belonging to a newly found subclass (2018)
  • Author(s): Masahiro Fujihashi, Tsutomu Sato, Yuma Tanaka, Daisuke Yamamoto, Tomoyuki Nishi, Daijiro Ueda, Mizuki Murakami, Yoko Yasuno, Ai Sekihara, Kazuma Fuku, Tetsuro Shinada and Kunio Miki,
  • Journal Title: Chemical Science Volume: 9 Issue: 15 Pages: 3754-3758
  • DOI: 10.1039/c8sc00289d
  • NAID: 120006466632
  • Peer Reviewed / Open Access
• [Journal Article] Isolation of biologically active peptides from the venom of Japanese carpenter bee, Xylocopa appendiculata. (2017)
  • Author(s): Kawakami, H., Goto, S., Murata, K., Matsuda, H., Shigeri, Y., Imura, T., Inagaki, H., and Shinada, T.
  • Journal Title: Journal of Venomous Animals and Toxins including Tropical Diseases Volume: 23 Issue: 1 Pages: 1-11
  • DOI: 10.1186/s40409-017-0119-6
  • Peer Reviewed / Open Access
• [Journal Article] Structure etermination of monomeric phloroglucinol derivatives with a cinnamoyl group isolated from propolis of the stingless bee, Tetragonula carbonaria (2016)
  • Author(s): Nishimura, E, Murakami, S., Suzuki, K., Amano, K., Tanaka, R., Shinada, T.
  • Journal Title: Asian Journal of Organic Chemistry Volume: in press Issue: 7 Pages: 855-859
  • DOI: 10.1002/ajoc.201600106
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Spectroscopic investigation of the carotenoid deoxyperidinin: direct observation of the forbidden S0 → S1 transition (2016)
  • Author(s): Greco, J. A., LaFountain, A. M., Kinashi, N., Shinada, T., Sakaguchi, K., Katsumura, S., S., Magdaong, S., Niedzwiedzki, D.M.R., Birge, R.H., Frank, A.
  • Journal Title: The Journal of Physiological Chemistry B Volume: 120 Issue: 10 Pages: 2731-2734
  • DOI: 10.1021/acs.jpcb.6b00439
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Facile synthesis of deuterium-labelled geranylgeraniols (2015)
  • Author(s): Totsuka, Y., Ueda, S., Kuzuyama, T. and Shinada, T.
  • Journal Title: Bulletin of the Chemical Society of Japan Volume: 88 Issue: 4 Pages: 575-577
  • DOI: 10.1246/bcsj.20140384
  • NAID: 130005064985
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] [4 + 2] Cyclization Reaction Using Trisubstituted Allyl Alcohols as Diene Precursors (2017)
  • Author(s): Yohei Toriyama, Ryota Ogura, Yoko Yasuno, Tetsuro Shinada
  • Organizer: 日本化学会第97回春季年会
  • Place of Presentation: 神奈川県横浜市、慶應義塾大学
  • Year and Date: 2017-03-16
• [Presentation] Large-terpene合成酵素の酵素的諸性質の解析と部位特異的変異 (2017)
  • Author(s): ○菅原啓、西智之、小川佳央、高橋宏忠、上田大次郎、藤橋雅宏、三木邦夫、保野陽子、品田哲郎、佐藤努
  • Organizer: 日本農芸化学会2018年度大会
• [Presentation] Large-terpene合成酵素の結晶構造解析 (2017)
  • Author(s): ○藤橋雅宏、佐藤 努、田中 勇真、山本 大輔、西智之、上田大次郎、村上瑞気、保野陽子、関原あい、福和真、品田哲郎、三木 邦夫
  • Organizer: 日本農芸化学会2018年度大会
• [Presentation] 微生物が生産する天然有機化合物の合成と機能解析 (2017)
  • Author(s): 品田哲郎
  • Organizer: 新潟大学コア・ステーション自然科学系附置植物・微生物科学研究センター共催公開セミナー
  • Invited
• [Presentation] 生命現象の解明に貢献する有機合成化学：オレフィンの立体制御を切り口として (2016)
  • Author(s): 品田哲郎
  • Organizer: 日本化学会中国四国支部岡山地区講演会
  • Place of Presentation: 岡山県岡山市、岡山大学
  • Invited
• [Presentation] 鎖状テルペン分子が先導する天然物化学 (2016)
  • Author(s): 品田哲郎
  • Organizer: 徳島文理大学薬学部セミナー
  • Place of Presentation: 徳島県徳島市、徳島文理大学
  • Invited
• [Presentation] テルペン酵素反応機構の解明を指向した重水素化プローブの選択的合成 (2015)
  • Author(s): 坂井健太、苅田祐馬、上田翔太、遠塚悠輔、保野陽子
  • Organizer: 第35回有機合成若手セミナー「明日の有機合成を担う人のために」
  • Place of Presentation: 京都府、京都市、京都府立大学
  • Year and Date: 2015-08-01
• [Remarks] 大阪市立大学大学院理学研究科物質分子系専攻分子変換学研究室
  • URL: http://www.sci.osaka-cu.ac.jp/chem/henkan/
• [Remarks] 大阪市立大学理学研究科物質分子系専攻分子変換学研究室
  • URL: http://www.sci.osaka-cu.ac.jp/chem/henkan/index.html
• [Remarks] 大阪市立大学分子変換学研究室
  • URL: http://www.sci.osaka-cu.ac.jp/chem/henkan/