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Study on The Establishment of Bioassay Systems for The Screening to Find Lead Compound for Drug Development

Research Project

Project/Area Number 08457583
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Chemical pharmacy
Research InstitutionTOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY

Principal Investigator

SANKAWA Ushio  TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY,Faculty of Phamaceutical Sciences, Professer, 薬学部, 教授 (60012613)

Co-Investigator(Kenkyū-buntansha) SHIBUYA Masaaki  Graduate School of Unv.Tokyo, Assistant Professer, 大学院・薬学系研究科, 助手 (50170923)
IWANAMI Naoko  TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY,Faculty of Phamaceutical Sciences,, 薬学部, 教務職員 (90283077)
HAYASHI Toshimitsu  TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY,Faculty of Pharmaceutical Sciences,, 薬学部, 助手 (40092796)
SHIMIZU Mineo  TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY,Faculty of Pharmaceutical Sciences,, 薬学部, 教授 (00019118)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥5,100,000 (Direct Cost: ¥5,100,000)
Fiscal Year 1997: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1996: ¥2,700,000 (Direct Cost: ¥2,700,000)
Keywordstyrosine kinase / cSrc / vSrc / interleukin-2 / interleukin-6 / herpes simplex virus / バイオアッセイ / 抗生物質 / 単純ヘルペスウイルス
Research Abstract

Inter and Intra-cellular signalings are inportant to maintain physiological function of living organisms. We have investigating natual products affecting inter- and intra-cellular signaling by a large scale screening, isolation and identification of bioactive natural products which have effects upon those signaling. 5-S-GAD_L (5-S-glutathionyl-b-alanyl-L-dopa) was first isolated as an antibiotic from insect infected with E.coli and later it was found that this compound possess inhibitory activity against self phosphorilation of vSrc tyrosine kinase. 5-S-GAD showed inhibitory activity in pit whole test with osteocrast cells. The synthesis of 5-S-GAD was rather easy when tyrosinase was used for the oxidation of dopa moiety to form ortho quinone which underwent Michel addition reaction with SH group of glutathione and its derivatives. Upto now beta-alanyl-L-dopa moiety was altered to beta-alanyl-D-dopa and beta-alanyl-L-methyldopa, and beta-alanyldopamine and dopamine. In the other hand g … More lutathione moiety was also converted into cystein, glycyl-cysteine and glutamyl-cysteine. The tyrosine kinase activity was determined three different assay methods, they are vSrc self phosphorilation with ^<32>P labelled ATP and the other is substrated phosphorilation against synthetic peptide consisting of Glu-Tyr or Rytide, a synthetic derivative of gastrine with recombinant cSrc. Inthibitory activity of 5-S-GAD derivatives are not completly pararel between self phosphorilation and substrate phosphorilation. Kinetic studies revealed these peptide like compounds are competitive against substrates. In addition to the inhibitors against tyrosine kinase, large scale sccreening works have been carried out on interleukin-2 and -6 by using cultured cells which release interleukins upon elicitation with ConA or interleukin 1. Bioassay on interleukins are possible to measure both inhibition and activaation. More than 2,000 samples of WAKANYAKU extracts and microbial cultutre broths are tested for their inhibitory activity against Herpes Simplex Virus infection to vero cells. The ratios of toxicity and anti-viral activity were used as indices and those showed more than 1000 was submitted for second screening. Valinomycine and concanamycins were identified as anti-HSV active substances and their reaction mechanis are now under investigation. Less

Report

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

    (27 results)

All Other

All Publications (27 results)

  • [Publications] Ushio Sankawa: "Molecular Cloning of Pea cDNA Encoding Cycloartenol Synthase" Biol.Pharm.Bull.20. 770-775 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ushio Sankawa: "Efficient Production of Biologically Active Diterpenoids" Phytochemistry. 46. 517-520 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Mineo Shimizu: "Antioxidative Activity of Flavones and Flavonols In Vivo" Phytotherapy Reserch. 11. 446-449 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Mineo Shimizu: "Paeoniflorin Ameliorates Acquisition Impairment" J.Traditional Medicines. 14. 163-168 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Toshimitsu Hayashi: "Antiviral activity of 5,6,7-trimetyhoxyflavone" J.Antimicrob.Chemother.39. 821-824 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Toshimitsu Hayashi: "Calcium spirulan as an inducer of tissue-type plasminogen activator" Biochim.Biophys.Acta.1355. 241-247 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ushio Sankawa: "Dynamic Aspects of Natural Products Chemistry" KODANSHA, 296 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ushio Sankawa: "Molecular Cloning of Pea cDNA Encoding Cycloartenol Synthase" Biol.Pharm.Bull.20. 770-775 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ushio Sankawa: "Efficient Production of Biologically Active Diterpenoids" Phytochemistry. 46. 517-520 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Mineo Shimizu: "Antioxidative Activity of Flavones and Flavonols In Vivo." Phytotherapy Res.11. 446-449 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Mineo Shimizu: "Paeoniflorin Ameliorates Acquisition Impairment" J.Trad.Medicines. 14. 163-168 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Toshimitsu Hayashi: "Antiviral activity of 5,6,7-trimetyhoxyflavone" J.Antimicrob.Chemother.39. 821-824 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Toshimitsu Hayashi: "Calcium spirulan as an inducer of tissue-type plasminogen activator" Biochim.Biophys.Acta.1355. 241-247 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ushio Sankawa: Dynamic Aspects of Natural Products Chemistry. KODANSHA, (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ushio Sankawa: "Molecular Cloning of Pea cDNA Encoding Cycloartenol Synthase" Biol.Pharm.Bull.20. 770-775 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ushio Sankawa: "Efficient Production of Biologically Active Diterpenoids" Phytochemistry. 46. 517-520 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Mineo Shimizu: "Antioxidative Activity of Flavones and Flavonols In Vivo." Phytotherapy Reserch. 11. 446-449 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Mineo Shimizu: "Paeoniflorin Ameliorates Acquisition Impairment" J.Traditional Medicines. 14. 163-168 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Toshimitsu Hayashi: "Antiviral activity of 5,6,7-trimetyhoxyflavone" J.Antimicrob.Chemother.39. 821-824 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Toshimitsu Hayashi: "Calcium spirulan as an inducer of tissue-type plasminogen activator" Biochim.Biophys.Acta.1355. 241-247 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ushio Sankawa: "Dynamic Aspects of Natural Products Chemistry" KODANSHA, 296 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ushio Sankawa :"Purification and Characterization of Sulochrin Oxidase" Chem.Pharm.Bull.19:. 42-46 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ushio Sankawa :"cDNA and Genomic DNA Cloning of Chalcone Synthase from Pueraria" Biol.Pharm.Bull.19:. 71-76 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ushio Sankawa :"Cloning of Chalcone-Flavanone Isomerase cDNA from Pueraria lobta" Protein Expression and Purification. 8:. 183-190 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ushio Sankawa :"Structural Determination of Bixin by Nuclear Magnetic Resonance Spectroscopy" Japanese Journal of Food Chemistry. 3:. 27-29 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Mineo Shimizu: "A New Triterpene Ester from Eribotrya japonica." Chem.Pharm.Bull.44:. 2181-2182 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tohsimitsu Hayashi :"Calcium spirulan,an inhibitor of enveloped virus replication" J.Nat.Prod.59:. 83-87 (1996)

    • Related Report
      1996 Annual Research Report

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

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