2013 Fiscal Year Final Research Report
Development of photochromic anti-cancer agent : kinesin Eg5 inhibitor
| Project/Area Number |
23650276
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Biomedical engineering/Biological material science
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| Research Institution | Soka University |
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Principal Investigator |
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| Project Period (FY) |
2011 – 2013
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| Keywords | ナノバイオロジー / ナノメディスン |
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| Research Abstract |
The mitotic kinesin Eg5 is essential for the formation of bipolar spindles during eukaryotic cell division, it has been considered as a potential target for cancer treatment. STLC is one of the inhibitors of Eg5 whose molecular mechanism of inhibition was well studied. In this study, we synthesized a novel photochromic STLC analogues, ACTAB, composed of a trityl group, azobenzene, and Acetyl-L-cysteine, which exhibits cis-trans photoisomerization in order to photocontrol the function of Eg5. ACTAB exhibited cis-trans photoisomerization upon alternating irradiation at two different visible wavelengths. ACTAB induced reversible changes in the inhibitory activity of ATPase and motor activities correlating with the cis-trans photoisomerization. Compared to cis-ACTAB, trans-ACTAB reduced ATPase activity and microtubule gliding velocity more significantly. These results suggest that ACTAB could be used as photochromic inhibitor of Eg5 to achieve photocontrol of living cells.
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[Journal Article] Nucleotide-dependent displacement and dynamics of the α-1 helix in kinesin revealed by site-directed spin labeling EPR2014
Author(s)
Yasuda, S., Yanagi, T., Yamada, M.D., Ueki, S., Maruta, S., Inoue A, & Arata T
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Journal Title
Biochem. Biophys. Res. Commun
Volume: 443
Pages: 911-916
Peer Reviewed
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