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Development of bioprobes which regulate mammalian cell cycle

Research Project

Project/Area Number07660128
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 応用微生物学・応用生物化学
Research InstitutionThe Institte of Physical and Chemical Research

Principal Investigator

OSADA Hiroyuki  The Institte of Physical and Chemical Research Chief Scientist, 抗生物質研究室, 主任研究員 (80160836)

Project Period (FY) 1995 – 1996
Project Status Completed(Fiscal Year 1996)
Budget Amount *help
¥2,200,000 (Direct Cost : ¥2,200,000)
Fiscal Year 1996 : ¥300,000 (Direct Cost : ¥300,000)
Fiscal Year 1995 : ¥1,900,000 (Direct Cost : ¥1,900,000)
Keywordscell cycle / taxol / cdc 2 kinase / inhibitor / tryprostration / acetophthalidin / 低分子プローブ / 真核細胞 / 微生物産物
Research Abstract

Cancer cells are uncontrolled cells with deregulation of the cell cycle, therefore, new cell cycle inhibitors might be good candidates for caner chemotherapy and also be a source for providing moleclar probes useful in elucidating regulatory mechanism of the cell cycle.
We have begun on the screening for new cell cycle inhibitors from microbial origin. During the screening, we have isolated novel diketopiperazine alkaloids, spirotryprostatins A,B,tryprostatins A,B and cyclotryprostatins B,D,together with three new natural diketopiperazines, cyclotryprostatins A,C and demethoxyfumitremorgin C,as well as several known diketopiperazines such as fumitremorgin C from the fermetation broth of a fungus, Aspergillus fumigatus BM939, through a separation procedure guided by inhibitory activity on the cell cycle progression of mouse tsFT210 cells. Compoiunds inhibited the cell cycle progression of tsFT210 cells at G2 or phase in the dose range of micromolar order.
Strctures of the new natural products obtained were determined mainly by the use of spectroscopic methods especially by detailed analyzes of their ^1H and ^<13>C NMR spectra with the aid of 2D NMR spectroscopy.

Report

(3results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report

Research Products

(56results)

All Other

All Publications

  • [Publications] Ubukata,M.,et al: "Sparoxomycine A1 and A2,new inducers of the flat reversion of NRK cells transformed by temperature sensitive rous sarcoma virus II.Isolation.……" J.Antibiot.49. 65-70 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nishiyama,U.,et al: "Structure activity relationship within a series of degradation products of tautomycin." Biosci.Biotech.Biochem.60. 103-107 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Cui,C,-B.,et al: "Acetophthalidin,a novel inhibitor of mammalian cell cycle,produced by a fungus isolated from a sea sediment." J.Antibiot.49. 216-219 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Isogai,Y.,et al: "Direct measurement of oscillatory generation of superoxide anions by single phagocytes." FEBS Lett.380. 263-266 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Matsuura,N.,et al: "Morphology reversion activity of phosmidosine and phosmidosine B,a newly isolated derivative,on src transformed NRK cells." J.Antibiot.49. 361-365 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Cui,C,-B.,et al: "Novel mammalian cell cycle inhibitors,tryprostatins A.B and other diketopiperazines produced by Aspergillus fumigatus I. Taxonomy.……" J.Antibiot.49. 527-533 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Cui,C.-B.,et al: "Novel mammalian cell cycle inhibitors,tryprostatins A.B and other diketopiperazines produced by Aspergillus fumigatus II. Physico-chemical properties and structure." J.Antibiot.49. 534-540 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Cui,Z.,et al: "The multidrug resistance associated protein (MRP) subfamily (Yrs1/Yor1) of saccharomyces cerevisiae is important for the tolerance to a broad rang of organic anions." J.Biol.Chem.271. 14712-14716 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Cui,C.-B.,et al: "Spirotryprostatin B,a novel mammalian cell cycle inhibitor produced by aspergillus fumigatus." J.Antibiot.49. 832-835 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Shimizu,T.,et al: "Synthetic studies on reveromycin A : stereoselective synthsis of the spiroketal system." Tetrahedron Lett.37. 6755-6758 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Cui,C.-B.,et al: "Novel mammalian cell cycle inhibitors,spirotryprostatins A and B,produced by Aspergillus fumigatus,which inhibit mammalian cell cycle at G2/M Phase." Tetrahedron.52. 12651-12666 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ubukata,M.,et al: "Sparoxomycins A1 and A2,new inducers of the flat reversion of NRK cells transformed by temperature sensitive rous sarcoma virus.I Taxonomy.……" J.Antibiot.49. 1096-1100 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Sudo,T.,et al: "Isolation and characterization of the gene encoding an aminopeptidase involved in the selective toxicity of ascamycin toward Xanthomonas campestris pv.citri." Biochem.J.319. 99-102 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Sodeoka,M.,et al: "Asymmetric synthesis of RK-682 and its analogs,and evaluation of their protein phosphatase inhibitory activities." Tetrahedron Lett.37. 8775-8778 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Cui,C.-B.,et al: "Novel mammalian cell cycle inhibitors. cyclotryprostatins A-D,produced by aspergillus fumigatus,which inhibit mammalian cell cycle at G2/M phase." Tetrahedron. 53. 59-72 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Osada,H.,et al: "Screening of cell cycle inhibitors from microbial metabolites by a bioassayusing a mouse cdc2 mutant cell line,tsFT210." Bioorg.Med.Chem.5. 193-203 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 長田裕之(分担): "分子腫瘍学「細胞周期と細胞内シグナル伝達の阻害剤の項目」" 中外医学社:佐藤昇志、菊地浩吉 編, 401-413 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ubukata, M., T.Morita, M.Uramoto & H.Osada: "Sparoxomycine A1 and A2, new inducers of the flat reversion of NRK cells transformed by temperature sensitive roous sarcoma virus. II.Isolation, Physico-chemical properties and structure elucidation" J.Antibiot. 49. 65-70 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nishiyama, U., M.Ubukata, J.Magae, T.Kataoka, F.Erdodi, J.H.D,K.Isono, K.Nagai & H.Osada: "Structureactivity relationship within a series of degradation products of tautomycin" Biosci. Biotech. Biochem. 60. 103-107 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Cui, C.B., M.Ubukata, H.Kakeya, R.Onose, G.Okada, I.Takahashi, K.Isono & H.Osada: "Acetophthalidin, a novel inhibitor of mammalian cell cycle, produced by a fungus isolated from a sea sediment" J.Antibiot. 49. 216-219 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Isogai, Y., T.Tsuyama, H.Osada, T.Iizuka & K.Tanaka: "Direct measrement of oscillatory generation of superoxide anions by single phagocytes" FEBS Lett.380. 263-266 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Matsuura, N., R.Onose & H.Osada: "Morphology reversion activity of phosmidosine and phosmidosine B,a newly isolated derivative, on src transformed NRK cells" J.Antibiot. 49. 361-365 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Cui, C.B., H.Kakeya, G.Okada, R.Onose & H.Osada: "Novel mammalian cell cycle inhibitors, tryprostatins A,B and other diketopiperazines produced by Aspergillus fumigatus I.Taxonomy, fermentaion, isolation and biological propertirs" J.Antibiot. 49. 527-533 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Cui, C.B., H.Kakeya & H.Osada: "Novel mammalian cell cycle inhibitors, tryprostatins A,B and other diketo piperazines produced by Aspergillus fumigatus II.Physico-chemical properties and structures" J.Antibiot. 49. 534-540 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Cui, Z., D.Hirata, E.Tsuchiya, H.Osada & T.Miyagawa: "The multidrug resistance associated protein (MRP) subfamily (Yrsl/Yorl) of saccharomyces cerevisiae is important for the tolerance to a broad rang of organic anions" J.Biol. Chemi.271. 14712-14716 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Cui, C.B., H.Kakeya & H.Osada: "Spirotryprostatin B,a novel mammalian cell cycle inhibitor produced by aspergillus fumigatus" J.Antibiot.49. 832-835 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Shimizu, T., R.Kobayashi, K.Osako, H.Osada & T.Nakata: "Synthetic studies on reveromycin A : stereoselective synthsis of the spiroketal system" Tetrahedron Lett.37. 6755-6758 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Cui, C.B., H.Kakeya & Osada: "Novel mammalian cell cycle inhibitors, spirotryprostatins A and B,produced by Aspergillus fumigatus, which inhibit mamalian cell cycle at G2/M Phase" Tetrahedron. 52. 12651-12666 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ubukata, M., T.Morita, H.Kakeya, K.Kobinata, T.Kudo & H.Osada: "Sparoxomycins A1 and A2, new inducers of the flat reversion of NRK cells transformed by temperature sensitive rous sarcoma virus. I.Taxonomy of the producing organism, fermentation and biological activity" J.Antibiot. 49. 1096-1100 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Suda, T., K.Shinohara, N., Dohmae, K.Takio, R.Usami, K.Horikoshi & H.Osada: "Isolation and characterization of the gene encoding an aminopeptidase involved in the selective toxicity of ascamycin toward Xanthomonas campestris pv. citri" Biochem. J.319. 99-102 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Sodeoka, M., R.Sampe, T.Kagemizono & H.Osada: "Asymmetric synthesis of RK-682 and its analogs, and evaluation of their protein phosphatase inhibitory activities" Tetrahedron Lett. 37. 8775-8778 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Cui, C.B., H.Kakeya & H.Osada: "Novel mammalian cell cycle inhibitors. cyclotyprostatins A D produced by aspergillus fumigatus, which inhibit mammalian cell cycle at G2/M phase" Tetrahedron. 53. 59-72 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Osada, H., Cui, C.B., Onose, R.and Hanaoka, F.: "Screening of cell cycle inhibitors from microbial metabolites by a bioassay using a mouse cdc2 mutant cell line, tsFT210" Bioorg. Med. Chem.5. 193-203 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ubukata,M.,et al: "Sparoxomycine A1 and A2. new inducers of the flat reversion of NRK cells transformed by temperature sensitive rous sarcoma virus II. Isolation. ……" J.Antibiot.49. 65-70 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nishiyama,U.,et al: "Structure-activity relationship within a series of degradation products of tautomycin." Biosci.Biotech.Biochem.60. 103-107 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Cui,C,B.,et al: "Acetophthalidin,a novel inhibitor of mamrualian cell cycle,produced by a fungus isolated from a sea sediment." J.Antibiot.49. 216-219 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Isogai,Y.,et al: "Direct measurement of oscillatory generation of superoxide anions by single phagocytes." FEBS Lett.380. 263-266 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Matsuura,N.,et al: "Morphology reversion activity of phosmidosine and phosmidosine B. a newly isolated derivative. on srctransformed NRK cells." J.Antibiot.49. 361-365 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Cui,C,-B.,et al: "Novel mammalian cell cycle inhibitors. tryprostatins A. B and other diketopiperazines produced by Aspergillus fumigatus I. Taxonomy. ……" J.Antibiot.49. 527-533 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Cui,C,-B.,et al: "Novel mammalian cell cycle inhibitors. tryprostatins A.B and other diketopiperazines produced by Asoergillus fumigatus II. Physico-chemical properties and structure." J.Antibiot.49. 534-550 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Cui,Z.,et al: "The multidrug resistance-associated protein (MRP) subfamily (Yrsi/Yorl) of saccharomyces cerevisiae is important for the tolerance to a broad rang of organic anions." J.Biol.Chem.271. 14712-14716 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Cui,C,-B.,et al: "Spirotryprostatin B. a novel mammalian cell cycle inhibitor produced by aspergillus fumigatus." J.Antibiot.49. 832-835 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Shimizu,T.,et al: "Synthetic studies on reveromycin A : stereoselective synthsis of the spiroketal system." Tetrahedron Lett.37. 6755-6758 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Cui,C,-B.,et al: "Novel mammalian cell cycle inhibitors,spirotryprostatins A and B. produced by Aspergillus Lumigatus,which inhibit mammalian cell cycle at G2/M Phase." Tetrahedron.52. 12651-12666 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ubukata,M.,et al: "Sparoxomycins A1 and A2. new inducers of the flat reversion of NRK cells transformed by temperature sensitive rous sarcoma virus. I Taxonomy. ……" J.Antibiot.49. 1096-1100 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Sudo,T.,et al: "Isolation and characterization of the gene encoding an aminopeptidase involved in the selective toxicity of ascamycin toward Xanthomonas campestris pv. citri." Biochem.J.319. 99-102 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Sodeoka,M.,et al: "Asymmetric synthesis of RK-682 and its analogs,and evaluation of their protein phosphatase inhibitory activities." Tetrahedron Lett.37. 8775-8778 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Cui,C.B.,et al: "Novel mammalian cell cycle inhibitors. cyclotryprostatins A-D. produced by aspergillus fumigatus,which inhibit mammalian cell cycle at G2/M phase." Tetrahedron. 53. 59-72 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Osada,H.,et al: "Screening of cell cycle inhibitors from microbial metabolites by a bioassay using a mouse cdc2 mutant cell line,tsFT210." Bioorg.Med.Chem.5. 193-203 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] 長田裕之(分担): "分子腫瘍学「細胞周期と細胞内シグナル伝達の阻害剤の項目」" 中外医学社:佐藤昇志、菊地浩吉編, 401-413 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Koshino, S., et al: "A new cyclic lipopeptide antibiotic, enamidonin" J. Antibiot. 48. 185-187 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Hamaguchi, T., et al: "RK-682, a potent inhibitor of tyrosine phosphatase, arrested the mammalian cell cycle progression at G1 phase." FEBS Lett.372. 54-58 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Ubukata, M., et al: "Preparation of optically active epiderstatin and its stereoisomers-epiderstatin is not a real inhibitor of mitogenic activity induced by epidermal growth factor." J. Antibioti,. 48. 1176-1178 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] B. R. Rani, et al: "Thiazoline analogues of epiderstatin, new inhibitors of cell cycle of tsFT-210 cells." J. Antibiot,. 48. 1179-1181 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Cui, C.-B., et al: "Tryprostatins A and B, novel mammalian cell cycle inhibitors produced by Aspergillus fumigatus." J. Antibiot,. 48. 1382-1384 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Osada, H.,: "Fascinating bioactive compounds from actinomycetes." Actinomycetlogica. 9. 254-262 (1995)

    • Related Report
      1995 Annual Research Report

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Published : 1995-04-01   Modified : 2016-04-21  

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