Optimizing Charge Switching in Membrane Lytic Peptides for Endosomal Release of Biomacromolecules.
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- Sakamoto, Kentarou
- Institute for Chemical Research, Kyoto University
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- Akishiba, Misao
- Institute for Chemical Research, Kyoto University
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- Iwata, Takahiro
- Institute for Chemical Research, Kyoto University
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- Murata, Kazuya
- Laboratory Animal Resource Center, Transborder Medical Research Center, Faculty of Medicine, University of Tsukuba
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- Mizuno, Seiya
- Laboratory Animal Resource Center, Transborder Medical Research Center, Faculty of Medicine, University of Tsukuba
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- Kawano, Kenichi
- Institute for Chemical Research, Kyoto University
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- Imanishi, Miki
- Institute for Chemical Research, Kyoto University
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- Sugiyama, Fumihiro
- Laboratory Animal Resource Center, Transborder Medical Research Center, Faculty of Medicine, University of Tsukuba
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- Futaki, Shiroh
- Institute for Chemical Research, Kyoto University
抄録
Endocytic pathways are practical routes for the intracellular delivery of biomacromolecules. Along with this, effective strategies for endosomal cargo release into the cytosol are desired to achieve successful delivery. Focusing on compositional differences between the cell and endosomal membranes and the pH decrease within endosomes, we designed the lipid-sensitive and pH-responsive endosome-lytic peptide HAad. This peptide contains aminoadipic acid (Aad) residues, which serve as a safety catch for preferential permeabilization of endosomal membranes over cell membranes, and His-to-Ala substitutions enhance the endosomolytic activity. The ability of HAad to destabilize endosomal membranes was supported by model studies using large unilamellar vesicles (LUVs) and by increased intracellular delivery of biomacromolecules (including antibodies) into live cells. Cerebral ventricle injection of Cre recombinase with HAad led to Cre/loxP recombination in a mouse model, thus demonstrating potential applicability of HAad in vivo.
収録刊行物
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- Angewandte Chemie International Edition
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Angewandte Chemie International Edition 59 (45), 19990-19998, 2020-11-02
Wiley
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キーワード
詳細情報
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- CRID
- 1050287142172199040
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- NII論文ID
- 120006954910
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- ISSN
- 14337851
- 15213773
- 15213757
- 00448249
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- HANDLE
- 2433/261198
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- Web Site
- https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fanie.202005887
- https://onlinelibrary.wiley.com/doi/pdf/10.1002/anie.202005887
- https://onlinelibrary.wiley.com/doi/full-xml/10.1002/anie.202005887
- https://onlinelibrary.wiley.com/doi/am-pdf/10.1002/anie.202005887
- https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fange.202005887
- https://onlinelibrary.wiley.com/doi/pdf/10.1002/ange.202005887
- https://onlinelibrary.wiley.com/doi/full-xml/10.1002/ange.202005887
- https://onlinelibrary.wiley.com/doi/am-pdf/10.1002/ange.202005887
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- 本文言語コード
- en
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- 資料種別
- journal article
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- データソース種別
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