2011 Fiscal Year Final Research Report
Fluorescent labeling of 14-3-3 proteins by fusicoccins
| Project/Area Number |
22655055
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Chemistry related to living body
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| Research Institution | Osaka University |
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Principal Investigator |
OHKANDA Junko 大阪大学, 産業科学研究所, 准教授 (50233052)
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| Project Period (FY) |
2010 – 2011
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| Keywords | 蛍光プローブ / 天然物 / リン酸化ペプチド / 14-3-3たんぱく質 / たんぱく質間相互作用 |
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| Research Abstract |
14-3-3 proteins play a critical role in serine/ threonine kinase-dependent signaling pathways through protein-protein interactions with multiple phosphorylated ligands. A ligand-dependent 14-3-3 detection technique would facilitate elucidation of 14-3-3-related intracellular signaling networks. Here, we describe phosphopeptide-dependent fluorescent labeling of 14-3-3. using cell penetrating probes derived from a diterpene natural product, fusicoccin. In vitro evaluations demonstrated that these compounds site-specifically attached a fluorescent tag onto the protein surface as a result of ternary complex formation with the 14-3-3 protein and a phosphopeptide ligand. The BODIPY-attached probe labeled human endogenous 14-3-3 in cancer cells under hyper-phosphorylation conditions, proving that 14-3-3 is a primary target of the fusicoccins in mammalian cells. This cell-penetrating labeling agent would be a useful tool to explore the mechanism of antitumor activity associated with fusicoccin-related agents.
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[Journal Article] A novel fusicoccin derivative prefentially targets hypoxic tumor cells and inhibits tumor growth in xenografts2012
Author(s)
K. Kawakami, M. Hattori, T. Inoue, Y. Maruyama, J. Ohkanda, N. Kato, M. Tongu, T. Yamada, M. Akimoto, K. Takenaga, T. Sassa, J. Suzumiya, Y. Honma
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Journal Title
Anti-cancer Agents in Medicinal Chemistry
Volume: (in press)
URL
Peer Reviewed
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