論文

査読有り
2020年6月18日

Optimizing charge switching in membrane lytic peptides for endosomal release of biomacromolecules

Angewandte Chemie (International ed. in English)
  • Kentarou Sakamoto
  • ,
  • Misao Akishiba
  • ,
  • Takahiro Iwata
  • ,
  • Kazuya Murata
  • ,
  • Seiya Mizuno
  • ,
  • Kenichi Kawano
  • ,
  • Miki Imanishi
  • ,
  • Fumihiro Sugiyama
  • ,
  • Shiroh Futaki

記述言語
掲載種別
研究論文(学術雑誌)
DOI
10.1002/anie.202005887

© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Endocytic pathways are practical routes for the intracellular delivery of biomacromolecules. Along with this, effective strategies for endosomal cargo release into cytosol are desired to achieve successful delivery. Focused 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 to enhance the endosomolytic activity. The ability of HAad to destabilize endosomal membranes was also supported by the 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, showing potential applicability of HAad in vivo.

リンク情報
DOI
https://doi.org/10.1002/anie.202005887
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/32557993
Scopus
https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85086733852&origin=inward
Scopus Citedby
https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85086733852&origin=inward

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