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タイトル: | Optimizing Charge Switching in Membrane Lytic Peptides for Endosomal Release of Biomacromolecules. |
著者: | Sakamoto, Kentarou Akishiba, Misao Iwata, Takahiro Murata, Kazuya Mizuno, Seiya Kawano, Kenichi https://orcid.org/0000-0003-1927-2922 (unconfirmed) Imanishi, Miki https://orcid.org/0000-0002-4172-0966 (unconfirmed) Sugiyama, Fumihiro Futaki, Shiroh |
著者名の別形: | 坂本, 健太郎 岩田, 恭宗 今西, 未来 河野, 健一 二木, 史朗 |
キーワード: | cationic peptides cell-penetrating peptides cytosolic delivery endosomal escape protein delivery |
発行日: | 2-Nov-2020 |
出版者: | Wiley |
誌名: | Angewandte Chemie International Edition |
巻: | 59 |
号: | 45 |
開始ページ: | 19990 |
終了ページ: | 19998 |
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. |
著作権等: | This is the peer reviewed version of the following article: K. Sakamoto, M. Akishiba, T. Iwata, K. Murata, S. Mizuno, K. Kawano, M. Imanishi, F. Sugiyama, S. Futaki, Angew. Chem. Int. Ed. 2020, 59, 19990, which has been published in final form at https://doi.org/10.1002/anie.202005887. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. The full-text file will be made open to the public on 20 August 2021 in accordance with publisher's 'Terms and Conditions for Self-Archiving'. This is not the published version. Please cite only the published version. この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。 |
URI: | http://hdl.handle.net/2433/261198 |
DOI(出版社版): | 10.1002/anie.202005887 |
PubMed ID: | 32557993 |
出現コレクション: | 学術雑誌掲載論文等 |
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