| Project/Area Number |
62430026
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Chemical pharmacy
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| Research Institution | The University of Tokyo |
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Principal Investigator |
SHUDO Koichi Fac. Pharm. Sci. Univ. Tokyo, Prof., 薬学部, 教授 (50012612)
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| 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)
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| Project Period (FY) |
1987 – 1989
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| Project Status |
Completed (Fiscal Year 1989)
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| 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)
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| Keywords | retinoid, 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 |
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| 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.
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