2013 Fiscal Year Final Research Report
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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| 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 |
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| 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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Research Products
(37 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
DOI
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)
Asako Mitsueda, Yuri Shimatani, Masahiro Ito, Takashi Ohgita, Asako Yamada, Susumu Hama, Astrid Gräslund, Staffan Lindberg, Ulo Langel, Hideyoshi Harashima, Ikuhiko Nakase, Shiroh Futaki, Kentaro Kogure
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Journal Title
Biopolymers (Peptide Science)
Volume: 100
Pages: 698-704
DOI
Peer Reviewed
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[Journal Article] Oligopeptides derived from autiphosphorylation sites of EGF receptor suppress EGF-stimulated responses in human lung carcinoma A549 cells2013
Author(s)
Yoshihiro Kuroda, Nahoko Kato-Kogoe, Emi Tasaki, Eri Murata, Koyo Ueda, Mineo Abe, Kazuhide Miyamoto, Ikuhiko Nakase, Shiroh Futaki, Yumi Tohyama, Munetaka Hirose
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Journal Title
European Journal of Pharmacology
Volume: 698
Pages: 87-94
DOI
Peer Reviewed
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[Journal Article] CXCR4 stimulates macropinocytosis : implications for cellular uptake of arginine-rich cell-penetrating peptides and HIV2012
Author(s)
Gen Tanaka, Ikuhiko Nakase, Yasunori Fukuda, Ryo Masuda, Shinya Oishi, Kazuya Shimura, Yoshimasa Kawaguchi, Tomoka Takatani-Nakase, Ülo Langel, Astrid Gräslund, Katsuya Okawa, Masao Matsuoka, Nobutaka Fujii, Yasumaru Hatanaka and Shiroh Futaki
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Journal Title
Chemistry & Biology
Volume: 19
Pages: 1437-1446
DOI
Peer Reviewed
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