| Project/Area Number |
23790129
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Drug development chemistry
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| Research Institution | Osaka Prefecture University (2013)
Kyoto University (2011-2012) |
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Principal Investigator |
NAKASE Ikuhiko 大阪府立大学, 21世紀科学研究機構, 講師 (40432322)
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| Project Period (FY) |
2011 – 2012
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Keywords | 膜透過性ペプチド / ミトコンドリア / 薬物送達 / アルギニン / エンドサイトーシス / アポトーシス |
|---|
| Research Abstract |
In this research, we demonstrated that the simple substitution of D-lysine with D-arginine in an artificial amphipathic helical peptide, KLA, which was originally designed as an antimicrobial peptide, considerably improved the membrane permeability of the peptide (RLA), and increased its mitochondrial accumulation without causing significant cytotoxicity. FITC-labeled RLA was efficiently taken up by HeLa cells ~40-fold higher than that of the KLA analyzed by flow cytometry. We also evaluated the mitochondrial delivery of a Bcl-xL BH4 domain peptide using RLA peptide. When the HeLa cells were treated with FITC-labeled RLA-BH4, marked colocalization of the fluorescent signals from cells was observed with mitochondrial structures. Additionally, pretreatment of RLA-BH4 resulted in effective suppression of apoptosis induced by etoposide. Thus, organelle-targeting is important for delivery of bioactive molecules, and the RLA peptide should provide a novel mitochondrial targeting method.
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