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1989 Fiscal Year Final Research Report Summary

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)
Project Period (FY) 1987 – 1989
Keywordsretinoid, differentiation, vitamin A, retinoic acid. teleocidin retinoid / differentiation / vitamin A / teleocidin / retinoic acid / active vitamin D / phorbol / proliferation
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.

  • Research Products

    (14 results)

All Other

All Publications (14 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
  • [Publications] 影近、他: "Retinobeuzoic acids 4.Corformation of Aromatic amides with retinoidal activity." J.Med.Chem. 32. 2292-2296 (1989)

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

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      「研究成果報告書概要(和文)」より
  • [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)

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

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

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

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

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

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

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  • [Publications] Shudo et al: Chemistry of carcinogenesis and carcinostatics.Hirokawa publishers.,

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Published: 1993-03-26  

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