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Peptide-Folding Triggered Phase Separation and Lipid Membrane Destabilization in Cholesterol-Rich Lipid Vesicles
[Image: see text] Liposome-based drug delivery systems are widely used to improve drug pharmacokinetics but can suffer from slow and unspecific release of encapsulated drugs. Membrane-active peptides, based on sequences derived or inspired from antimicrobial peptides (AMPs), could offer means to tri...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9026255/ https://www.ncbi.nlm.nih.gov/pubmed/35362952 http://dx.doi.org/10.1021/acs.bioconjchem.2c00115 |
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author | Utterström, Johanna Barriga, Hanna M. G. Holme, Margaret N. Selegård, Robert Stevens, Molly M. Aili, Daniel |
author_facet | Utterström, Johanna Barriga, Hanna M. G. Holme, Margaret N. Selegård, Robert Stevens, Molly M. Aili, Daniel |
author_sort | Utterström, Johanna |
collection | PubMed |
description | [Image: see text] Liposome-based drug delivery systems are widely used to improve drug pharmacokinetics but can suffer from slow and unspecific release of encapsulated drugs. Membrane-active peptides, based on sequences derived or inspired from antimicrobial peptides (AMPs), could offer means to trigger and control the release. Cholesterol is used in most liposomal drug delivery systems (DDS) to improve the stability of the formulation, but the activity of AMPs on cholesterol-rich membranes tends to be very low, complicating peptide-triggered release strategies. Here, we show a de novo designed AMP-mimetic peptide that efficiently triggers content release from cholesterol-containing lipid vesicles when covalently conjugated to headgroup-functionalized lipids. Binding to vesicles induces peptide folding and triggers a lipid phase separation, which in the presence of cholesterol results in high local peptide concentrations at the lipid bilayer surface and rapid content release. We anticipate that these results will facilitate the development of peptide-based strategies for controlling and triggering drug release from liposomal drug delivery systems. |
format | Online Article Text |
id | pubmed-9026255 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-90262552022-04-25 Peptide-Folding Triggered Phase Separation and Lipid Membrane Destabilization in Cholesterol-Rich Lipid Vesicles Utterström, Johanna Barriga, Hanna M. G. Holme, Margaret N. Selegård, Robert Stevens, Molly M. Aili, Daniel Bioconjug Chem [Image: see text] Liposome-based drug delivery systems are widely used to improve drug pharmacokinetics but can suffer from slow and unspecific release of encapsulated drugs. Membrane-active peptides, based on sequences derived or inspired from antimicrobial peptides (AMPs), could offer means to trigger and control the release. Cholesterol is used in most liposomal drug delivery systems (DDS) to improve the stability of the formulation, but the activity of AMPs on cholesterol-rich membranes tends to be very low, complicating peptide-triggered release strategies. Here, we show a de novo designed AMP-mimetic peptide that efficiently triggers content release from cholesterol-containing lipid vesicles when covalently conjugated to headgroup-functionalized lipids. Binding to vesicles induces peptide folding and triggers a lipid phase separation, which in the presence of cholesterol results in high local peptide concentrations at the lipid bilayer surface and rapid content release. We anticipate that these results will facilitate the development of peptide-based strategies for controlling and triggering drug release from liposomal drug delivery systems. American Chemical Society 2022-04-01 2022-04-20 /pmc/articles/PMC9026255/ /pubmed/35362952 http://dx.doi.org/10.1021/acs.bioconjchem.2c00115 Text en © 2022 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Utterström, Johanna Barriga, Hanna M. G. Holme, Margaret N. Selegård, Robert Stevens, Molly M. Aili, Daniel Peptide-Folding Triggered Phase Separation and Lipid Membrane Destabilization in Cholesterol-Rich Lipid Vesicles |
title | Peptide-Folding Triggered Phase Separation and Lipid
Membrane Destabilization in Cholesterol-Rich Lipid Vesicles |
title_full | Peptide-Folding Triggered Phase Separation and Lipid
Membrane Destabilization in Cholesterol-Rich Lipid Vesicles |
title_fullStr | Peptide-Folding Triggered Phase Separation and Lipid
Membrane Destabilization in Cholesterol-Rich Lipid Vesicles |
title_full_unstemmed | Peptide-Folding Triggered Phase Separation and Lipid
Membrane Destabilization in Cholesterol-Rich Lipid Vesicles |
title_short | Peptide-Folding Triggered Phase Separation and Lipid
Membrane Destabilization in Cholesterol-Rich Lipid Vesicles |
title_sort | peptide-folding triggered phase separation and lipid
membrane destabilization in cholesterol-rich lipid vesicles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9026255/ https://www.ncbi.nlm.nih.gov/pubmed/35362952 http://dx.doi.org/10.1021/acs.bioconjchem.2c00115 |
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