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Development of neuropeptide antagonists witha multipeptide synthesizer and application of the antagonists

Research Project

Project/Area Number 08454269
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 動物生理・代謝
Research InstitutionHIROSHIMA UNIVERSITY

Principal Investigator

MUNEOKA Yojiro  Hiroshima University, Faculty of Integrated Arts and Sciences, Professor, 総合科学部, 教授 (40031330)

Co-Investigator(Kenkyū-buntansha) FUJISAWA Yuko  Hiroshima University, Faculty of Integrated Arts and Sciences, Research associat, 総合科学部, 助手 (80274025)
TSUTSUI Kazuyoshi  Hiroshima University, Faculty of Integrated Arts and Sciences, Professor, 総合科学部, 教授 (20163842)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥5,200,000)
Fiscal Year 1997: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1996: ¥3,400,000 (Direct Cost: ¥3,400,000)
KeywordsNeuropeptide / APGWamide / APGWGNamide / Multipeptide synthesizer / Combinatrial chemistry / Opioid peptide / Agoinst / Antagonist / コンビナトリアル化学 / 軟体動物 / 脊椎動物 / ヒドラ / ウズラ / イガイ抑制性ペプチド / GLWamide / ガラニン
Research Abstract

1. Approximately 70 species of bioactive peptides (mostly neuropeptides) were isoland from various animals in five phyla (Chidaria, Annelida, Mollusca, Echinodermata and Choldata) using their muscles as bioassay systems, and their structures were determined. The peptides were synthesized and their functions were examined. Among these peptides, the mollluscan neuropeptides APGWamide and MIPs (Mytilus inhibitory peptides) were chosen as the subject peptides for development of agonists and antagonists of their receptors.
2. According to the combinatrial chemistry method, a number of oligopeptide libralies were synthesized with a multipeptide synthesizer. The libralies were subjected to establish a method for isolation of bioactive peptides in them. In this preliminary experiments for development of agonists and antagonists, numbers of bioactive peptides including a novel potent analgesic peptide with an unnatural amino acid were obtained.
3. According to the method established in the preliminary experiments, many agonists and antagonists of the receptors of APGWamide and MIPs were developed. Among these ligands, the autagonist APGWGNamide was suggested to be an useful experimental tool to clarify the functions of neural systems in which APGWamide is involved.

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (52 results)

All Other

All Publications (52 results)

  • [Publications] Masahiro Ohtani: "Isolation of neurotensin-related bioactive peptides from peptide libraries synthesized with a multipeptide synthesizer" Peptide Chemistry 1995,Ed.by N.Nishi. 181-184 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kazuyoshi Ukena: "Inhibitory pentapeptides isolated from the gut of the Earthworm,Eisenia foetida" Comp.Biochem.Physiol.114A. 245-249 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yuko Fujisawa: "Immunohistochemical localization and Ca^<2+>-dependent release of mytilus inhibitory peptides in the ABRM of Mytilus edulis" Zool.Sci.13. 795-801 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Masahiro Ohtani: "pQVPLPRYamide isolated from the clam Meretrix lusoria:a member of a novel molluscan reuropeptide family" Peptide Chemistry 1996,Ed.by C.Kitada. 117-120 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Masahiro Ohtani: "Isolation of bioactive peptides from Wamide-peptide libraries synthesized with a multipeptide synthesizer" Peptide Chemistry 1996,Ed.by C.Kitada. 205-208 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Toshio Takahashi: "Structure-activity relation of LWamide peptides synthesized with a multipeptide synthesizer" Peptide Chemistry,Ed.by C.Kitada. 193-196 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Masahiro Ohtani: "Isolation of bioactive compounds from Helix aspersa nerve tissue and the effect of pOPPLPRYamide on heart esophagus and central neurons of H.aspersa and rectum of Anodonta" Gen.Pharmacol.29. 103-111 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kazuyoshi Tsutsui: "Demonstration,localization,and development of galanin receptors in the quail oviduct" J.Exp.Zool. 277. 57-65 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Toshio Takahashi: "Systematic isolation of peptide signal molecules regulating development in hydra:LWamide and PW families" Proc.Natl.Acad.Sci.USA. 94. 1241-1246 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Chikafumi Chiba: "Time course of appearance of GABA and GABA receptors during retinal regeneration in the adult rewt" Develop.Brain Res.98. 204-210 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hiroyuki Minakata: "The leechexcitatory peptide,a member of the GGNG peptide family:isolation and comparison with the earthworm GGNG peptides" FEBS Letters. 410. 437-442 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Takashi Niida: "Characterization of binding of the annelidan myoactive peptides GGNG peptides,to tissues of the earthworm,Eisenia foetida" J.Exp.Zool.279. 562-570 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Fumihiro Morishita: "A novel D-amino-acid-containing peptide isolated from aplysia heart" Biochem.Biophys.Res.Commun.240. 354-358 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] S.M.Pedder: "Structural requirements and ionic mechanism of the Mytilus inhibitory peptides (MIPs) on helix central reurons" Gen.Pharmacol.30. 213-220 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 宗岡 洋二郎: "神経ペプチドの比較生物学" 化学と生物. 36. 153-159 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Masahiro Ohtani: "Isolation and characterization of bioactive peptides from the sea cucumber,Stichopus japonicus" Proceedings of the 1st International Peptide Symposium,Ed.by Y.Shimonishi. (in press). (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Iori Maeda: "Identification of a novel analgesic peptide including an unnatural amino acid from peptide libraries synthesized with a multipeptide synthesizer" Proceedings of the 1st.International Peptide Symposium.Ed.by Y.Shimonishi. (in press). (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Masaaki Fujimoto: "Isolation and characterization of a novel bioactive peptide,carassius RFamide (C-RFa),from the brain of the japanese rucian carp" Biochem.Biophys.Res.Commun.(in press). (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] R.Birenheide: "Peptides controlling stiffiness of connective tissue in sea cucumber" Biol.Bull.(in press). (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Toshio Takahashi: "Identification of a novel member of LWamide family in a hydra and physiological activity and localization of LWamides" Biol.Bull.(in press). (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M.Ohtani, Y.Muneoka, N.Kanemoto, K.Ogino, Y.Masui and S.Aimoto: "Isolation of neurotensinrelated bioactive pentapeptides from peptide libraries synthesized with a multipeptide synthesizer." Peptide Chemistry 1995, N.Nishi (Ed.), Protein Research Foundatio Osaka. 181-184 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Ukena, T.Oumi, O.Matsushima, T.Takahashi, Y.Muneoka, T.Fujita, H.Minakata and K.Nomoto: "Inhibitory pentapeptides isolated from the gut of the earthworm, Eisenia foetida." Comp.Biochem.Physiol.114A. 245-249 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Y.Fujisawa: "Immunohistochemical localization and Ca-dependent release of Mytilus inhibitory peptides in the ABRM of Mytilus edulis." Zool.Sci.13. 795-801 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M.Ohtani, Y.Fujisawa, Y.Muneoka, T.Takao and Y.Shimonishi: "pQVPLPRYamide isolated from the clam Meretrix lusoria : a member of a novel molluscan neuropeptide family." Peptide Chemistry 1996, C.Kitada (Ed.), Protein Research Foundation Osaka. 117-120 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M.Ohtani, Y.Muneoka, N.Kanemoto, K.Ogino, Y.Masui and S.Aimoto: "Isolation of bioactive peptides from Wamide-peptide libraries synthesized with a multipeptide synthesizer." Peptide Chemistry 1996, C.Kitada (Ed.), Protein Research Foundation Osaka. 205-208 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] T.Takahashi, M.Ohtani, Y.Muneoka, S.Aimoto, M.Hatta, H.Shimizu, T.Fujisawa, T.Sugiyama and O.Koizumi: "Structure-activity relation of LWamide peptides synthesized with a multipeptide synthesizer." Peptide Chemistry 1996, C.Kitada (Ed.), Protein Research Foundation Osaka. 193-196 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M.Ohtani, Y.Muneoka, O.Matsushima, T.Takao, Y.Shimonishi, A.R.White, S.Pedder, R.Sharma, M.A.Lennon, S.Katugampola and R.J.Walker: "Isolation of bioactive compounds from Helix aspersa nerve tissue and the effect of pQPPLPRYamide on esophagus and central neurons of H.aspersa and rectum of Anodonta woodiana." Gen.Pharmac.29. 103-111 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Tsutsui, D.Li, Y.Azimaya, Y.Muneoka, H.Minakaata and K.Nomoto: "Demonstration, localization, and development of galanin receptors in the quail oviduct." J.Exp.Zool.277. 57-65 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] T.Takahashi, Y.Muneoka, J.Lohman, M.S.de Haro, G.Solleder, T.C.G.Bosch, C.N.David, H.R.Bode, O.Koizumi, H.Shimizu, M.Hatta, T.Fujisawa and T.Sugiyama: "Systematic isolation of peptide signal molecules regulating development in hydra : LWamide and PW families." Proc.Natl.Acad.Sci.USA 94. 1241-1246 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] C.Chiba, O.Matsushima, Y.Muneoka and T.Saito: "Time course of appearance of GABA and GABA receptors during retinal regeneration in the adult newt." Develop.Brain.Res.98. 204-210 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] H.Minakata, T.Fujita, T.Kawano, T.Nagahama, T.Oumi, K.Ukena, O.Matsushima, Y.Muneoka and K.Nomoto: "The leech excitatory peptide, a member of the GGNG peptide family : isolation and comparison with the earthworm GGNG peptides." FEBS Letters. 410. 437-442 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] T.Niida, T.Nagahama, T.Oumi, K.Ukena, F.Morishita, K.Tsutsui, M.Ohtani, Y.Muneoka, T.Fujita, T.Kawano, H.Minakata and K.Nomoto: "Characterization of binding of the annelidan myoactive peptides, GGNG peptides, to tissues of the earthworm, Eisenia foetida." J.Exp.Zool.279. 562-570 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] F.Morishita, Y.Nakanish, S.Kaku, Y.Furukawa, S.Ohta, T.Hirata, M.Ohtani, Y.Fujisawa, Y.Muneoka and O.Matsushima: "A novel D-amino-acid-containing peptide isolated from Aplysia heart." Biochem.Biophys.Res.Commun.240. 354-358 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] S.M.Pedder, M.L.Chen, Y.Muneoka and R.J.Walker: "Structural requirements and ionic mechanism of the Mytilus inhibitory peptides (MIPs) on Helix central neurons." Gen.Pharmac.30. 213-220 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Y.Muneoka: "Comparative aspects of neuropeptides." KASEAA. 36. 153-159 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M.Ohtani, E.Iwakoshi, Y.Muneoka, H.Minakata and K.Nomoto: "Isolation and characterization of bioactive peptides from the sea cucumber, Stichopus japonicus." Proceedings of the 1st International Peptide Symposium, Y.Shimonishi (Ed.), Kluwer Academic Publishers B.V., The Netherlands. (in press). (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] I.Maeda, N.Kanemoto, K.Ogino, M.Kuwahara, Y.Goto M.Adachi, T.Taki, M.Ohtani, Y.Muneoka, T.Kawakami, and S.Aimoto: "Identification of a novel analgesic peptide including an unnatural amino acid from peptide libraries synthesized with a multipeptide synthesizer." Proceedings of the 1st International Peptide Symposium, Y.Shimonishi (Ed.), Kluwer Academic Publishers B.V., The Netherlands. (in press). (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M.Fujimoto, K.Takeshita, X.Wang, I.Takabatake, Y.Fujisawa, H.Teranishi, M.Ohtani, Y.Muneoka and S,Ohta: "Isolation and characterization of a novel bioactive peptide, carassius RFamide (C-RFa), from the brain of the Japanese crucian carp." Biochem.Biophys.Res.Commun.(in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] R.Birenheide, M.Tamori, T.Motokawa, M.Ohtani, E.Iwakoshi, Y.Muneoka, T.Fujita, H.MInakata and K.Nomoto: "Peptides controlling stiffness of connective tissue in sea cucumber." Biol.Bull.(in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] T.Takahashi, Y.Kobayakawa, S.Mohri, M.Hatta, T.Fujisawa, T.Sugiyama, Y.Muneoka and O.Koizumi: "Identification of a novel member of LWamide family in a hydra and physiological activity and localization of LWamides." Biol.Bull.(in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 宗岡洋二郎: "神経ペプチドの比較生物学" 化学と生物. 36. 153-159 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Fumihiro Morishita: "A novel D-amino-acid-containing peptide isolated from Aplysia heart" Biochem.Biophys.Res.Commun.240. 354-358 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Takashi Niida: "Characterization of binding of the annelidan myoactive peptides,GGNG peptides,to tissues of the earthworm,Eisenia foetida" J.Exp.Zool.279. 562-570 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Masahiro Ohtani: "Isolation and characterization of bioactive peptides from the sea cucumber,Stichopus japonicus" Proceedings of the 1st International Peptide Symposium,Ed.by Y.Shimonishi. (in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Iori Maeda: "Identification of a novel analgesic peptide including an unnatural amino acid from peptide libraries synthesized with a multi-peptide synthesizer" Proceedings of the 1st International Peptide Symposium,Ed.by Y.Shimonishi. (in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Masaaki Fujimoto: "Isolation and characterization of a novel bioactive peptide,carassius RFamide (C-RFa),from the brain of the Japanese" Biochem.biophys.Res.Commun.(in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Masahiro Ohtani: "Isolation of neurotensin-related bioactive pentapeptides from peptide libraries synthesized with a multipeptide synthesizer" Peptide Chemistry 1995. 181-184 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Masahiro Ohtani: "Isolation of bioactive peptidesfrom Wamide-peptide libralies synthesized with a multipeptide synthesizer" Peptide Chemistry 1996. (In press).

    • Related Report
      1996 Annual Research Report
  • [Publications] Toshio Takahash: "Structure-activity relation of LWamide peptides synthesized with a multipeptide synthesizer" Peptide Chemistry 1996. (In press).

    • Related Report
      1996 Annual Research Report
  • [Publications] Toshio Takahash: "Systematic isolation of peptide signal molecules regulating development in hydra : LWamide and PW families" Proc. Natl. Acad. Sci. USA. (In press).

    • Related Report
      1996 Annual Research Report
  • [Publications] Kazuyoshi Tsutsui: "Demonstration, localization and development of galanin receptors in the quail oviduct" J. Exp. Zool.(In press).

    • Related Report
      1996 Annual Research Report
  • [Publications] Yuko Fujisawa: "Immunohistochemical localizationi and Ca2+-dependent release of Mytilus inhibitory peptides in the ABRM of Mytilus edulis" Zool. Sci.13. 795-801 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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