Identification of peptide ligands for lipid receptors

• Project/Area Number: 21570128
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Gunma University
• Principal Investigator: TAKEDA Shigeki 群馬大学, 大学院・工学研究科, 教授 (80282854)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: Gタンパク質共役受容体 / TGR5 / GPCR-Gα融合タンパク質 / ランダムペプチドライブラリー

Research Abstract

A random hexapeptide library was screened to identify novel peptide ligands for a TGR5, which is a G-protein-coupled receptor for bioactive steroids. We successfully identified a weak agonist peptide (Ac-WLFLHV-NH2 ) with EC50 of 630 nM, and a weak antagonist peptide (Ac-WVFLIV-NH2) with IC50 of 15 nM.

Research Products

• [Journal Article] 5-Hydroxyntaed is an endogenous GPR119 agonist and enhances glucose-dependent insulin secretion (2011)
  • Author(s): R. Kogure, K. Toyama, S. Hiyamuta, I. Kojima, S. Takeda
  • Journal Title: Biochem. Biophys. Res. Commun. Biochem. Volume: 416 Pages: 58-63
  • Peer Reviewed
• [Journal Article] Genomic and proteomic chaacterization of the large Myoviridae bacteriophage TMA of the extreme thermophile (2011)
  • Author(s): M. Tamakoshi, A. Murakami, M. Sugisawa, K. Tsuneizumi, S. Takeda, T. Saheki, T. Izumi, T. Akiba, K. Mitsuoka, H. Toh, A. Yamashita, F. Arisaka, M. Hattori, T. Oshima, A. Yamagishi
  • Journal Title: Thermus thermophilus, Bacteriophage Volume: 67 Pages: 837-841
  • Peer Reviewed
• [Journal Article] The host-binding domain of the P2 phage tail spike reveals a trimericiron-binding structure (2011)
  • Author(s): E. Yamashita, A. Nakagawa, J. Takahashi, K. Tsunoda, S. Yamada, S. Takeda
  • Journal Title: Acta Cryst. F Volume: 67 Pages: 837-841
• [Journal Article] The host-binding domain of the P2 phage tail spike reveals a trimeric iron-binding structure (2011)
  • Author(s): E.Yamashita, et al.
  • Journal Title: Acta Cryst.F Volume: 67 Pages: 837-841
  • Peer Reviewed
• [Journal Article] Genomic and proteomic characterization of the large Myoviridae bacteriophage φTMA of the extreme thermophile Thermus thermophilus (2011)
  • Author(s): M.Tamakoshi, et al.
  • Journal Title: Bacteriophage Volume: 1 Pages: 152-164
  • Peer Reviewed
• [Journal Article] 5-Hydroxy-eicosapentaenoic acid is an endogenous GPR119 agonist and enhances glucose-dependent insulin secretion (2011)
  • Author(s): R.Kogure, et al.
  • Journal Title: Biochem.Biophys.Res.Commun..Biochem. Volume: 385 Pages: 58-63
  • Peer Reviewed
• [Journal Article] The C-terminal domain is sufficient for host-bindingactivity of the Mu phage tail-spike protein (2010)
  • Author(s): H. Suzuki, S. Yamada, Y. Toyama, S. Takeda
  • Journal Title: Biochim Biophys Acta Volume: 1804 Pages: 1738-1742
• [Journal Article] The host-binding domain of the P2 phage tail spike reveals a trimeric iron-binding structure (2010)
  • Author(s): E.Yamashita, et. al.
  • Journal Title: Acta Cryst.F1 Volume: in press
  • Peer Reviewed
• [Journal Article] Observation of the membrane binding activity and domain structure of gpV, which comprises the tail spike of bacteriophage P2 (2009)
  • Author(s): Y. Kageyama, M. Murayama, T. Onodera, S. Yamada, H. Fukada, M. Kudou, K. Tsumoto, Y. Toyama, S. Kado, K. Kubota, S. Takeda
  • Journal Title: Biochemistry Volume: 48 Pages: 10129-10135
  • Peer Reviewed
• [Journal Article] Efficient Silkworm Expression of Human GPCR (Nociceptin Receptor) by a Bombyx mori Bacmid DNA System (2009)
  • Author(s): M. Kajikawa, K. Sasaki, Y. Wakimoto, M. Toyooka, T. Motohashi, T. Shimojima, S. Takeda, Y. Park, K. Maenaka
  • Journal Title: Biochem. Biophys. Res. Commun. Biochem Volume: 385 Pages: 375-379
  • Peer Reviewed
• [Journal Article] Production and characterization of the recombinant human -opioid receptor from transgenic silkworms (2009)
  • Author(s): M. Tateno, M. Toyooka, Y. Shikano, S. Takeda, N. Kuwabara, H. Sezutsu, T. Tamura
  • Journal Title: J. Biochem.(Tokyo) Volume: 145 Pages: 37-42
  • Peer Reviewed
• [Journal Article] The N-terminal domain of GPR61, an orphan G protein-coupled receptor, is essential for its constitutive activity (2009)
  • Author(s): M. Toyooka, T. Tsujii, S. Takeda
  • Journal Title: J. Neursci. Res Volume: 87 Pages: 1329-1333
  • Peer Reviewed
• [Journal Article] The N-terminal domain of GPR61, an orphan G protein-coupled receptor, is essential for its constitutive activity (2009)
  • Author(s): M.Toyooka, et al.
  • Journal Title: J.Neurosci.Res. 87 Pages: 1329-1333
  • Peer Reviewed
• [Journal Article] Production and characterization of the recombinant human μ-opioid receptor from transgenic silkworms (2009)
  • Author(s): M.Tateno, et al.
  • Journal Title: J.Biochem.(Tokyo) 145 Pages: 37-42
  • Peer Reviewed
• [Journal Article] Efficient Silkworm Expression of Human GPCR(Nociceptin Receptor)by a Bombyx mori Bacmid DNA System (2009)
  • Author(s): M.Kajikawa, et al.
  • Journal Title: Biochem.Biophys.Res.Commum..Biochem. 385 Pages: 375-379
  • Peer Reviewed
• [Journal Article] Observation of the membrane binding activity and domain structure of gpV, which comprises the tail spike of bacteriophage P2 (2009)
  • Author(s): Y.Kageyama, et al.
  • Journal Title: Biochemistry 48 Pages: 10129-10135
  • Peer Reviewed
• [Presentation] Purification and characeriatin of gp45, a basepate subunit for bacteriophage Mu, and its mutants (2011)
  • Author(s): 上野貴志, 外山吉治, 武田茂樹
  • Organizer: 日本分子生物学会
  • Year and Date: 2011-12-16
• [Presentation] Identification of a new insulin secretion inducer and determinaon of its receptor (2011)
  • Author(s): 木暮亮太, 遠山和矢, 小島至, 冷牟田修一, 武田茂樹
  • Organizer: 日本分子生物学会
  • Year and Date: 2011-12-16
• [Presentation] Identification of a new insulin secretion inducer and determination of its receptor (2011)
  • Author(s): R.Kogure, et al.
  • Organizer: 第34回日本分子生物学会
  • Place of Presentation: パシフィコ横浜(横浜)
  • Year and Date: 2011-12-16
• [Presentation] Purification and characterization of gp45, a baseplate subunit for bacteriophage Mu, and its mutants (2011)
  • Author(s): T.Ueno, et al.
  • Organizer: 第34回日本分子生物学会
  • Place of Presentation: パシフィコ横浜(横浜)
  • Year and Date: 2011-12-16
• [Presentation] 遺伝子組換えカイコを用いたオピオイドμ受容体-Giα融合タンパク質の発現と活性評価 (2011)
  • Author(s): 二階堂良亮, 他
  • Organizer: 第34回日本分子生物学会
  • Place of Presentation: パシフィコ横浜(横浜)
  • Year and Date: 2011-12-13
• [Presentation] バクテリオファージMu基盤サパンブユニットgp45変異体の精製と解析 (2011)
  • Author(s): 上野貴志, 外山吉治, 武田茂樹
  • Organizer: 日本化学会関東支部群馬地区地域懇談会
  • Year and Date: 2011-12-10
• [Presentation] バクテリオファージMu基盤サブユニットgp45変異体の精製と解析 (2011)
  • Author(s): 上野貴志, 他
  • Organizer: 日本化学会関東支部群地区地域懇談会
  • Place of Presentation: 群馬大学工学部(桐生)
  • Year and Date: 2011-12-10
• [Presentation] インスリン分泌を促進する化合物の探索とそれに関与する受容体の同定 (2011)
  • Author(s): 木暮亮太, 他
  • Organizer: 日本化学会関東支部群馬地区地域懇談会
  • Place of Presentation: 群馬大学工学部(桐生)
  • Year and Date: 2011-12-10
• [Presentation] Muファージのテールスパイクタンパク質gp45のC末端のX線構造解析 (2011)
  • Author(s): 原田健, 他
  • Organizer: 日本結晶学会年会
  • Place of Presentation: 北海道大学学術交流会館(札幌)
  • Year and Date: 2011-11-24
• [Presentation] Identification of Novel Peptide Agonists from a Random Peptide Library for a G Protein Coupled Receptor (2011)
  • Author(s): S.Takeda, et al.
  • Organizer: ,BIT' s 9th Annual Congress of International Drug Discovery Science and Technology (IDDST)-2011
  • Place of Presentation: Shenzhen, China
  • Year and Date: 2011-11-02
• [Presentation] EPA代謝物にみられた新規生理活性の解析 (2011)
  • Author(s): 武田茂樹, 他
  • Organizer: 第10回生命科学研究会
  • Place of Presentation: ホテルメトロポリタン高崎(高崎)
  • Year and Date: 2011-06-24
• [Presentation] 「カイコによるヒト・動物医薬品開発」の近況報告 (2011)
  • Author(s): 武田茂樹
  • Organizer: ファイブロバイオ工学セミナー
  • Year and Date: 2011-02-18
• [Presentation] カイコ発現系を用いたオピオイドμ受容体T4L融合タンパク質(MOR-T4L)の発現と可溶化 (2010)
  • Author(s): 大崎真希, 武田茂樹, 若松馨
  • Organizer: 分子生物学会
  • Year and Date: 2010-12-08
• [Presentation] バクテリオファージMu基盤タンパク質gp46のX線結晶解析に向けた精製 (2010)
  • Author(s): 金澤悠子, 武田茂樹, 津本浩平
  • Organizer: 分子生物学会
  • Year and Date: 2010-12-08
• [Presentation] GPR84の機能解析を目指したアゴニスト探索 (2010)
  • Author(s): 小山雄大, 武田茂樹, 岡部隆義
  • Organizer: 分子生物学会
  • Year and Date: 2010-12-07
• [Presentation] GPR84の機能解析を目指したアゴニスト探索 (2010)
  • Author(s): 小山雄大、武田茂樹, 他
  • Organizer: 日本分子生物学会
  • Place of Presentation: 兵庫県・神戸市
  • Year and Date: 2010-12-07
• [Presentation] バクテリオファージMu基盤タンパク質gp46のX線結晶解析に向けた精製 (2010)
  • Author(s): 金澤悠子、武田茂樹, 他
  • Organizer: 日本分子生物学会
  • Place of Presentation: 兵庫県・神戸市
  • Year and Date: 2010-12-07
• [Presentation] カイコ発現系を用いたオピオイドμ受容体T4L融合タンパク質(MOR-T4L)の発現と可溶化 (2010)
  • Author(s): 大崎真希、武田茂樹, 他
  • Organizer: 日本分子生物学会
  • Place of Presentation: 兵庫県・神戸市
  • Year and Date: 2010-12-07
• [Presentation] 遺伝子改変カイコによるヒトオピオイド受容体の発現とその解析 (2010)
  • Author(s): 武田茂樹
  • Organizer: 日本繊維機械学会関東支部
  • Year and Date: 2010-11-24
• [Presentation] インスリン分泌を促進する化合物の探索と、それに関与する受容体の同定 (2010)
  • Author(s): 木暮亮太, 遠山和矢, 小島至, 冷牟田修一, 武田茂樹
  • Organizer: 日本化学会関東支部群馬地区地域懇談会
  • Year and Date: 2010-11-05
• [Presentation] 生物内でのたんぱく質の超分子構造 (2010)
  • Author(s): 武田茂樹
  • Organizer: 高分子学会関東支部茨城・群馬・栃木地区合同活動講演会
  • Year and Date: 2010-11-05
• [Presentation] P2ファージテイルスパイクタンパク質gpVの解析 (2010)
  • Author(s): 武田茂樹
  • Organizer: 大阪大学蛋白質研究所セミナー
  • Year and Date: 2010-09-09
• [Presentation] アゴニスト結合型5-oxo-ETE受容体モデルの変異体を用いた検証 (2010)
  • Author(s): 武田茂樹、田中麻衣
  • Organizer: 日本脂質生化学会
  • Place of Presentation: 群馬・渋川市
  • Year and Date: 2010-06-14
• [Presentation] G protein-coupled receptor and insulin secretion ; Drug screening for type 2 diabetes (2010)
  • Author(s): 武田茂樹
  • Organizer: 国際内分泌学会大会
  • Place of Presentation: 京都
  • Year and Date: 2010-03-30
• [Book] 4u(フォーユー) (2009)
  • Author(s): 武田茂樹
  • Total Pages: 2
  • Publisher: 首都圏北部4大学連合
• [Remarks]
  • URL: http://chem-bio.gunma-u.ac.jp/~stakeda-lab/index.html
• [Remarks]
  • URL: http://takedalab.bce.gunma-u.ac.jp
• [Remarks]
  • URL: http://chem-bio.gunma-u.ac.jp/~stakeda-lab/index.html
• [Remarks]
  • URL: http://takedalab.bce.gunma-u.ac.jp
• [Patent(Industrial Property Rights)] GPR119アゴニスト並びにそれを含むインスリン分泌促進剤、血糖降下剤および糖尿病治療または予防剤 (2011)
  • Inventor(s): 冷牟田修一、武田茂樹、小島至
  • Industrial Property Rights Holder: 出光興産
  • Industrial Property Number: 2011-201858
  • Filing Date: 2011-09-15