| Project/Area Number |
08558067
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Bioorganic chemistry
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| Research Institution | TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY |
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Principal Investigator |
SANKAWA Ushio TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY,Faculty of Phamarceutical Sciences, Professer, 薬学部, 教授 (60012613)
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| Co-Investigator(Kenkyū-buntansha) |
佐藤 俊次 (株)ツムラ, 研究所, 次長
SHIBUYA Masaaki Graduate School of Unv.Tokyo, Assistant Professer, 薬学部, 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 Phamarceutical Sciences,, 薬学部, 助手 (40092796)
SHIMIZU Mineo TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY,Faculty of Phamarceutical Sciences,, 薬学部, 教授 (00019118)
SATO Tsoshitsugu Tsumura Company, Central Inst., Division Chief
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥9,700,000 (Direct Cost: ¥9,700,000)
Fiscal Year 1997: ¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 1996: ¥5,800,000 (Direct Cost: ¥5,800,000)
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| Keywords | tyrosine kinase / vSrc / cSrc / interleukin-2 / interleukin-6 / herpes simplex virus / 単純ヘルペスウイルス / 放線菌 |
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| Research Abstract |
Inter and Intra-cellular signalings are inportant to maintain physiological function of living organisms. We have investigating natual products affection 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.coil 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
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