1990 Fiscal Year Final Research Report Summary
Studies on the Role of Poly (ADP-ribosyl) Action in Cell Differentiation and Oncogenesis
| Project/Area Number |
01480146
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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 Univ. Fac. of Med., Dept. of Lab. Med. Assoc. Prof., 医学部・臨床検査医学講座, 助教授 (00027070)
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| Project Period (FY) |
1989 – 1990
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| Keywords | Poly (ADP-ribose) synthetase / cDNA cloning / DNA binding / Homology profile / Inhibitor / Naphthalimide / Vitamin K / Tetratocarcinoma |
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| Research Abstract |
1. Cloning of cDNA coding for poly (ADP-ribose) synthetase : A complete amino acid sequence of bovine poly (ADP-ribose) synthetase was determined by cDNA cloning. A comparison of the sequence with those of human and mouse enzymes revealed that various structural units (e. g., Zn-binding fingers) important to enzymatic functions such as DNA-binding, automodification, and NAD-binding have been almost completely conserved throughout evolution. For the use of homology analysis at levels of regions or domains, we invented a new plot termed "homology profile".
2. Discovery of specific inhibitors of poly (ADP-ribosyl) action : From among 300 compounds tested, we found a number of potent inhibitors of poly (ADP-ribose) synthetase, including 1,8-naphthalimide, 6 (5H) -phenanthridinone, 1-hydroxyisoquinoline, their derivatives, and 4-hydroxyquinazoline ; theywee more potent and specific than known inhibitors such as nicotinamide and benzamide derivatives. We also found that vitamin K as well as novobiocin was much more specific for mono- than poly (ADP-ribosyl) action.
3. Induction of tumor cell differentiation : We succeeded in inducing differentiation of teratocarcinoma cells in culture by administrating our new inhibitors of poly (ADP-ribosyl) ation, such as 4-hydroxyquinazoline and arachidonic acid.
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