Development of mitochondria-targeted cell-penetrating peptide for intracellular delivery
| 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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Report
(4 results)
Research Products
(74 results)
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[Journal Article] Curvature engineering: positive membrane curvature induced by epsin N-terminal peptide boosts internalization of octaarginine2013
Author(s)
Silvia Pujals, Hiroki Miyamae, Sergii Afonin, Tomo Murayama, Hisaaki Hirose, Ikuhiko Nakase, Kentaro Taniuchi, Masato Umeda, Kazutami Sakamoto, Anne S. Ulrich, Shiroh Futaki
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Journal Title
ACS Chemical Biology
Volume: 8
Pages: 1894-1899
Related Report
Peer Reviewed
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[Journal Article] Development of a novel nanoparticle by dual modification with the pluripotential cell-penetrating peptide PepFect6 for cellular uptake, endosomal escape, and decondensation of an siRNA core complex2013
Author(s)
Mitsueda A, Shimatani Y, Ito M, Ohgita T, Yamada A, Hama S, Gräslund A, Lindberg S, Langel U, Harashima H, Nakase I, Futaki S, Kogure K
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Journal Title
Biopolymers
Volume: Vol.100
Issue: 6
Pages: 698-704
DOI
Related Report
Peer Reviewed
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[Journal Article] Collagen-like cell-penetrating peptides2013
Author(s)
Chisato M. Yamazaki, Ikuhiko Nakase, Hiroyuki Endo, Saya Kishimoto, Yoshihiro Mashiyama, Ryo Masuda, Shiroh Futaki, Takaki Koide
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Journal Title
Angewandte Chemie International Edition
Volume: 52
Issue: 21
Pages: 5497-5500
DOI
Related Report
Peer Reviewed
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[Journal Article] Oligopeptides derived from autophosphorylation sites of EGF receptor suppress EGF-stimulated responses in human lung carcinoma A549 cells.2013
Author(s)
Kuroda Y, Kato-Kogoe N, Tasaki E, Murata M, Ueda K, Abe M, Miyamoto K, Nakase I, Futaki S, Tohyama Y, Hirose M
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Journal Title
Eur J Pharmacol
Volume: 698
Issue: 1-3
Pages: 87-94
DOI
Related Report
Peer Reviewed
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[Journal Article] Transient Focal Membrane Deformation Induced by Arginine-rich Peptides Leads to Their Direct Penetration into Cells2012
Author(s)
Hirose, H., Takeuchi, T., Osakada, H., Pujals, S., Katayama, S., Nakase, I., Kobayashi, S., Haraguchi, T., Futaki, S
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Journal Title
Molecular Therapy
Volume: (in press)
Issue: 5
Pages: 984-993
DOI
Related Report
Peer Reviewed
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