| Project/Area Number |
61480122
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
General medical chemistry
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| Research Institution | Kyoto University |
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Principal Investigator |
UEDA Kunihiro Kyoto University Faculty of Medicine, 医学部, 助教授 (00027070)
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| Project Period (FY) |
1986 – 1987
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| Project Status |
Completed (Fiscal Year 1987)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥6,500,000)
Fiscal Year 1987: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1986: ¥5,000,000 (Direct Cost: ¥5,000,000)
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| Keywords | Poly(ADP-ribose) / Myelogenous leukemia / Poly(ADP-ribose) synthetase inhibitors / Induction of cancer cell differentiation / Teratocarcinoma / Microinjection / Spermatogenesis / グルタミルボースー5-リン酸蓄積症 / 細胞分化 / 分化誘導 / フレンド赤白血病細胞 / 抗ポリ(ADP-リボース)抗体 |
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| Research Abstract |
1. Analysis of changes in poly(ADP-ribose) synthesizing activity during cell differentiation: Disappearance of the synthetase activity during maturation of myelocytes was confirmed with many cases of myelogenous leukemia.
2. Discovery and analysis of new inhibitors of poly(ADP-ribose) synthetase: By a survey of more than 200 compounds, many new and potent inhibitors of the synthetase were discovered, including analogues of known inhibitors and derivatives of completely different chemical structures. A structure-activity relationship of these inhibitors was also studied.
3. Induction of cancer cell differentiation by suppression of poly(ADP-ribose) synthesis: One of the new inhibitors of synthetase, i.e. 4-hydroxyquinazoline, was shown to induce differentiation of teratocarcinoma cells.
4. Analysis with microinjection technique: Microinjection of anti-poly(ADP-ribose) antibody into Friend's erythroleukemia cells failed to induce differentiation to hemoglobin-producing cells.
5. Analysis of differentiation-associated changes in gene expression: Progressive disappearance of poly(ADP-ribose) synthetase during spermatogenesis was observed in rat testis.
6. Other analysis: Studies on glutamyl ribose-5-phosphate storage disease and on cDNA for poly(ADP-ribose) synthetase were also carried out.
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