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Title: Optimizing Charge Switching in Membrane Lytic Peptides for Endosomal Release of Biomacromolecules.
Authors: Sakamoto, Kentarou
Akishiba, Misao
Iwata, Takahiro
Murata, Kazuya
Mizuno, Seiya
Kawano, Kenichi  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0003-1927-2922 (unconfirmed)
Imanishi, Miki  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0002-4172-0966 (unconfirmed)
Sugiyama, Fumihiro
Futaki, Shiroh
Author's alias: 坂本, 健太郎
岩田, 恭宗
今西, 未来
河野, 健一
二木, 史朗
Keywords: cationic peptides
cell-penetrating peptides
cytosolic delivery
endosomal escape
protein delivery
Issue Date: 2-Nov-2020
Publisher: Wiley
Journal title: Angewandte Chemie International Edition
Volume: 59
Issue: 45
Start page: 19990
End page: 19998
Abstract: 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.
Rights: 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(Published Version): 10.1002/anie.202005887
PubMed ID: 32557993
Appears in Collections:Journal Articles

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