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Design and synthesis of μ-selective opioidomimetic peptides

Research Project

Project/Area Number 11694326
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 医薬分子機能学
Research InstitutionKobe Gakuin University

Principal Investigator

OKADA Yoshio  Kobe Gakuin University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (60068236)

Co-Investigator(Kenkyū-buntansha) TSUDA Yuko  Kobe Gakuin University, Faculty of Pharmaceutical Sciences, Assistant Professor, 薬学部, 講師 (10098478)
YOKOI Toshio  Kobe Gakuin University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (50122255)
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 2001: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2000: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1999: ¥800,000 (Direct Cost: ¥800,000)
Keywordsopioid mimetics / pyrazinone derivatives / endomorphine derivatives / diamine derivartives / dimethyltyrosine / μ-opioid receptor agoniat / 鎮痛薬 / 皮下投与 / オピオイドミナティクス / エンドモルーフィン誘導体 / δ-オピオイドレセプターアンタゴニスト / 二機能性リガンド
Research Abstract

This project started as International Scientific Research by The Ministry of Education, Culture, Sports, Science and Technology in 1999 and then as Grant-in-Aid for Scientific Research (C) in 2000 and 2001. Therefore, Dr. Lawrence H. Lazarus and Ms. Sharon D. Bryant of National Institute of Environmental Health Sciences, USA were investigators in this project. Dr. Yoshio Okada has been engaged in synthesis of peptides based on the peptide synthesis we made a plan of this project with objective to develop novel type of anti-pain medicine, and obtained following results. 1) We could develop synthetic methodologies ofpeptides. 2) We designed and synthesized endomorphin derivatives and obtained compounds which exhibited potent μ-opioid receptor agonistic activity and δ-opioid receptor antagonistic activity. We designated them as bifunctional opioid mimetics. 3) Employing new method to synthesize pyrazinones from dipeptidyl chloromethyl ketones, novel type opioid memetics containing pyrazinone ring were prepared. 4) Instead of pyrazinone ring, NH_2(CH_2)nNH_2 (n=2-8)were employed to prepare novel types of anti-pain drugs. 5) Compounds obtained above exhibited more potent in vitro and in vivo activity than morphine.6) International conference Annual ' Conference on Opioid Mimetic Analgesics 2002" was successfully held from 17 to 19 of March, 2002 at Awaji Yumebutai International Conference Center and we exchanged our mutual interest concerning the developme t of anti-pain medicines."

Report

(4 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] Yoshio Okada et al.: "Amino Acids and Peptides. LVI. Synthesis of pyrazinone ring-containing opioid mimetics and examination of their opioid receptor binding activity"Tetrahedron. 55. 14391-14406 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yoshio Okada et al.: "Synthesis of pyrazinone ring-containing opioid mimetics and examination of their opioid receptor binding activity"Chem.Pharm.Bull.. 47. 1193-1195 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yoshio Okada et al.: "Synthesis of Stereoisomeric Analogues of Endomorphin-2, H-Tyr-Pro-Phe Phe-NH_2, and Examination of Their Opioid Receptor Binding Acitivities"Biocheim.Biophys.Res.Commun.. 276. 7-11 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yoshio Okada: "Synthesis of Peptides by Solution Methods"Current Organic Chemistry. 5. 1-43 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yoshio Okada: "Huben-Weyl Methods of Organic Chemistry, Volume E 22a : Synthesis of Peptides and Peptidomimetics"Thieme Stuttgart-New York. 901 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yoshio Okada, Atsuko Fukumizu, Motohiro Takahashi, Junpei Yamazaki, Toshio Yokoi, Yuko Tsuda, Sharon D.Bryant, Lawrence H.Lazarus: "Amino Acids and Peptides.LVI.Synthesis of pyrazinone ring-containing opioid mimetics and examination of their opioid receptor binding activity"Tetrahedron. 55. 14391-14406 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yoshio Okada, Atsuko Fukumizu, Motohiro Takahashi, Junpei Yamazaki, Toshio Yokoi, Yuko Tsuda, Sharon D.Bryant, Lawrence H.Lazarus: "Synthesis of Pyazinone ring-containing Opioid Mimetics and Examination of their Opioid Receptor Bbinding activity"Chem. Pharm. Bull. 47. 1193-1195 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yoshio Okada, Atsuko Fukumizu, Motohiro Takahashi, Yoshiro Shimizu, Yuko Tsuda, Toshio Yokoi, Sharon D.Bryant, Lawrence H.Lazarus: "Synthesis of Stereoismeric Analogues of Enfomorphin-2, H-Tyr-Pro-Phe-Phe-NH_2, and Examination of Their Opioid Receptor Binding Activities and Solution Conformation"Biochem. Biophys. Res. Commun. 276. 7-11 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yoshio Okada: "Synthesis of Peptides by Solution methods"Current Organic Chemistry. 5. 1-43 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yoshio Okada: "Synthesis of Peptides in Solution"Huben-Weyl Methods of Chemistry, Volume E22a : Synthesis of Peptides and Peptidomimetics Thieme Stuttgart-New York. 591-626 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tadashi Okamoto, Takashi Matsuya, Takeo Kishi, and Kiyota Goshima: I Experimental Methods of Cultured Cells, 5 Experimental Method of Cultured Cardiac myocytes. Experimental Methods of Cell Biology Hirokawa Publishing Co.. 59-71 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y.Okada et al.: "Computational chemistry and opioidmimetics : Receptor-ligand interactions of three classes of biologically potent peptides"Peptides 2000. 407-408 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Y.Okada et al.: "Development of bifunctional opioid ligands containing dimethyltyrosine"Peptieds 2000. 753-754 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Y.Okada et al.: "Synthesis ofendornorphin-2 analogues, studies on their activities for opioid receptors, and three dimensional structure"Peptide Sciences 2001. 105-108 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Y.Okada et al.: "Synthesis of opiold mimetics containing a pyrazinone ring and their activities"Peptide Sciences 2001. 143-146 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Y.Okada: "Synthesis of Peptides by Solution Method"Current Oganic Chemistry. 5. 1-43 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Y.Okada: "Synthesis Peptiudes and Peptidomimetics"Thieme Stuttgart-New York. 594-626 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yoshio Okada et al: "Synthesis of Stereoisomeric Analogue-"Biochem.Biophys.Res.Commun.. 276.1. 7-11 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yoshio Okada,L.H.Lazarus: "Synthesis of Pyrazinone Ring-Containing--"Chemical Pharmaceutical Bulletin. 47(8). 1193-1195 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Y.Okada,L.H.Lazarus: "Amino Acids and Peptides.LVI.Synthesis--"Tetrahedron. 55(50). 14391-14406 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Y.Okada,L.H.Lazarus: "Synthesis of Endomorphine Analogs and Studies"Peptide Science 1998. 197-200 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Y.Okada,L.H.Lazarus: "Design and Synthesis of Pyrazinone Ring-"Peptide Sciences 1998. 313-316 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Y.Okada,L.H.Lazarus: "Synthesis of Endomorphin Analogs and--"Peptide 1998. 684-685 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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