2003 Fiscal Year Final Research Report Summary
Studies for Structure-Activities Relationships of Reveromycin A : An Inhibitor of Eukaryotic Cell Growth
| Project/Area Number |
14572104
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
医薬分子機能学
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| Research Institution | RIKEN (The Institute of Physical and Chemical Research) |
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Principal Investigator |
SHIMIZU Takeshi RIKEN (The Institute of Physical and Chemical Research), Synthetic Organic Chemistry Laboratory, Senior Scientist, 有機合成化学研究室, 副主任研究員 (80087569)
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| Co-Investigator(Kenkyū-buntansha) |
MACHIDA Kiyotaka RIKEN (The Institute of Physical and Chemical Research), Antibiotic Laboratory, Contract Researcher, 抗生物質研究室, 協力研究員 (30332266)
USUI Takeo RIKEN (The Institute of Physical and Chemical Research), Antibiotic Laboratory, Research Scientist, 抗生物質研究室, 研究員 (60281648)
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| Project Period (FY) |
2002 – 2003
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| Keywords | reveromycin A / 6,6-spiroacetal / tri-carboxylic acids / inhibitor of eukaryotic cell growth / anti-tumor agent / inhibitor of protein synthesis / therapeutic drug for hypercalcemia / bioprobe |
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| Research Abstract |
Reveromycin A is a novel polyketide-type antibiotic produced by Streptomyces sp. and inhibits mitogenic activity induced by the epidermal growth factor in a mouse epidermal keratinocyte. The characteristic structural features of reveromycin A include a 1,7-dioxaspiro[5.5]undecane moiety, that is, the 6,6-spiroacetal system bearing a hemisuccinate, two alkenyl carboxylic acids, and methyl and n-butyl groups. Various derivatives of reveromycin A were prepared and their inhibitory effects on both isoleucyl-tRNA synthetase activity and in vitro protein synthesis, and activities on the morphological reversion of src^<ts> NRK cells were assayed. It was clarified that the C5 hydroxyl group and C24 carboxyl group were particularly important for these activities.
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Research Products
(4 results)
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[Publications] Miyamoto Y, Machida K, Mizunuma M, Emoto Y, Sato N, Miyahara K, Hirata D, Usui T., Takahashi H, Osada H, Miyakawa T.: "Identification of Saccharomyces cerevisiae isoleucyl-tRNA synthetase as a target of the G1-specific inhibitor Reveromycin A"J.Biol.Chem.. 277. 28810-28814 (2002)
Description
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