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Chemical studies on specific regulatory molecules of cell proliferation and differentiation.

Research Project

Project/Area Number 62430026
Research Category

Grant-in-Aid for General Scientific Research (A)

Allocation TypeSingle-year Grants
Research Field Chemical pharmacy
Research InstitutionThe University of Tokyo

Principal Investigator

SHUDO Koichi  Fac. Pharm. Sci. Univ. Tokyo, Prof., 薬学部, 教授 (50012612)

Co-Investigator(Kenkyū-buntansha) ENDO Yasuyuki  Fac. Pharm. Sci. Univ. Tokyo, Lecturer, 薬学部, 講師 (80126002)
OHNO Masaji  Fac. Pharm. Sci. Univ. Tokyo, Prof., 薬学部, 教授 (00111550)
IITAKA Yoichi  Fac. Pharm. Sci. Univ. Tokyo, Prof., 薬学部, 教授 (90012591)
KOGA Kenji  Fac. Pharm. Sci. Univ. Tokyo, Prof., 薬学部, 教授 (10012600)
SANKAWA Ushio  Fac. Pharm. Sci. Univ. Tokyo, Prof., 薬学部, 教授 (60012613)
大和田 智彦  東京大学, 薬学部, 助手 (20177025)
Project Period (FY) 1987 – 1989
Project Status Completed (Fiscal Year 1989)
Budget Amount *help
¥30,700,000 (Direct Cost: ¥30,700,000)
Fiscal Year 1989: ¥4,600,000 (Direct Cost: ¥4,600,000)
Fiscal Year 1988: ¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 1987: ¥19,100,000 (Direct Cost: ¥19,100,000)
Keywordsretinoid, differentiation, vitamin A, retinoic acid. teleocidin retinoid / differentiation / vitamin A / teleocidin / retinoic acid / active vitamin D / phorbol / proliferation / 活性ビタミンD3 / ビタミンA酸 / レセプター / 構造活性相関 / 核内レセプター / 分化誘導物質 / 血球分化 / 芳香族アミド / アフィディコリン / サイトカイニン / ペプチド / cーcmyc
Research Abstract

This project aimed to study specific regulatory molecules of cell differentiation and cell proliferation from the standpoint of organic chemistry.
The first result includes the chemistry and biochemistry of retinoids. We have prepared a number of specific inducers of human promyelocytic leukemia cells to granulocytes. These compounds are proved to be classified as retinoids. Studies on structure-activity relationships of these synthetic retinoids revealed the essential moieties in the molecules for the activity. Stereochemical studies also suggested the importance of linear structure of the retinobenzoic acids.
In relation to the mechanism of action of retinoids, we identified the receptor proteins of retinoic acid which are coded by RAR-a and RAR-b genes which belong to the onco-gene erb-A kamily.
Another project on regulators was related to the tumor promoter receptor. Phorbol ester which is a strong tumor promoter binds to cytosolic protein different from protein kinase C. This protein translocates to nuclear in the presence of the phorbol ester. Extensive study for the redeptor is progressing, in particular structural elucidation of the protein is mostimportant.
In relation to the tumor promotion, synthetic and activity studies have been performed. This also suggested the receptor cavity model for tumor promoters.

Report

(4 results)
  • 1989 Annual Research Report   Final Research Report Summary
  • 1988 Annual Research Report
  • 1987 Annual Research Report
  • Research Products

    (33 results)

All Other

All Publications (33 results)

  • [Publications] 大和田、他: "Etylene Dicetions Substituted with Electron donating groups" J.Org Chem. 54. 5227-5237 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 影近、他: "Retinobeuzoic acids 4.Corformation of Aromatic amides with retinoidal activity." J.Med.Chem. 32. 2292-2296 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 影近、他: "Retinobenzoic acids 2.Structure activity relationships of Chalcone carboxylic acids" J.Med.Chem. 32. 834-840 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 首藤、他: "DNAの化学修飾と発がんGln-P-Iによる発がんの初期過程" 癌と化学療法. 16. 445-450 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 橋本、他: "Retinoic acid receptors α and β are expressed in the human promyelocytic cells" Molecular Endocrinology. 3. 1046-1052 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 橋本、他: "遺伝子発現を制御するビタミンA酸" 現代化学. 39. 39-45 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 首藤、他: "発がんと制がんの化学(印刷中)" 広川書店, (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Ohwada et al: "Ethylene dications substituted with electron withdrawing groups." J. Org. Chem.54. 5227-5237 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Kagechika et al: "Retinobenzoic acids 4. Conformation of aromatic amides with retinoidal activity." J. Med. Chem. 32, 1989 2292-2296.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Kagechika et al: "Retinobenzoic acids. 2. Structure-activity relationships of chalcone-carboxylic acids." J. Med. Chem. 32, 1989, 834-840.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Shudo et al: "DNA-chemical modification and carcinpgenesis. Initial events of carcinogenesis by GluPl." Gann to Kagakuryoho 16.1989, 4450450 (in Japanese).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Hashimoto et al: "Retinoic acid receptors a and b are expressed in the human promyelocytic leukemia cells." Mol. Endocr. 3, 1989, 1046-1052.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Hashimoto et al: "Retinoic acid regulates gene expression." Gendai Kagaku 39, 1989, 39-45.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Shudo et al: Chemistry of carcinogenesis and carcinostatics.Hirokawa publishers.,

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 大和田他: "Etylene Dications Substituted with Electron-Donating Groups" J.Org.Chem.54. 5227-5237 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 影近他: "Retinobenzoic Acids.4. Conformation of Aromatic Amides with Retinoidal Activity" J.Med.Chem.32. 2292-2296 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 影近他: "Retinobenzoic Acids.2.Structure-Activity relationships of Chalcone carboxylic Acids." J.Med.Chem.32. 834-840 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 首藤他: "DNAの化学修飾と発がんGluーpー1による発ガンの初期過程" 癌と化学療法. 16. 445-450 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 橋本他: "Retinoic Acid receptors alpha and beta are expressed in the human promyelocytic cells" Molecular Endocrinology. 3. 1046-1052 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 橋本他: "遺伝子発現を制御するビタミンA酸" 現代化学. 39. 39-45 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 首藤他: "発がんと制がんの化学" 広川書店,

    • Related Report
      1989 Annual Research Report
  • [Publications] 首藤紘一 他: 化学と生物. 12. 802-803 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 遠藤泰之 他: Proc.Natl.Acad.Sci.(USA). 85. 3688-3692 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 首藤紘一 他: Life Chemistry Reports. 6. 231-265 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 首藤紘一 他: Biochem.Biorhys.Res.Com.155. 503-508 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 大和田智彦 他: J.Am.Chem.Soc.110. 1862-1870 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 首藤紘一 他: Tetoahedron Letters. 29. 6279-6282 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 首藤 紘一: 化学と生物. 25. 5-7 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] 首藤 紘一: ファルマンア レビュー. 43. 51-62 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] 遠藤 泰之: テトラヘドロン. 43. 3645-3704 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] 大和田 智彦: アメリカ化学会誌. 109. 7036-7041 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] 古賀 憲司: 純正応用化学連合誌(Pure,Appl,Chlm). 1987.

    • Related Report
      1987 Annual Research Report
  • [Publications] 板井 昭子: Proc.Natl.Acad.Sci (USA). 1988.

    • Related Report
      1987 Annual Research Report

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Published: 1987-04-01   Modified: 2018-02-02  

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