Peptide-Folding Triggered Phase Separation and Lipid Membrane Destabilization in Cholesterol-Rich Lipid Vesicles
| العنوان: | Peptide-Folding Triggered Phase Separation and Lipid Membrane Destabilization in Cholesterol-Rich Lipid Vesicles |
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| المؤلفون: | Johanna Utterström, Hanna M. G. Barriga, Margaret N. Holme, Robert Selegård, Molly M. Stevens, Daniel Aili |
| المساهمون: | Royal Academy Of Engineering |
| المصدر: | Bioconjugate Chemistry. 33:736-746 |
| بيانات النشر: | American Chemical Society (ACS), 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Pharmacology, 0304 Medicinal and Biomolecular Chemistry, Lipid Bilayers, Organic Chemistry, Biomedical Engineering, Pharmaceutical Science, Bioengineering, 0601 Biochemistry and Cell Biology, 0305 Organic Chemistry, Cholesterol, Drug Delivery Systems, Liposomes, lipids (amino acids, peptides, and proteins), Peptides, Biotechnology |
| الوصف: | 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. |
| تدمد: | 1520-4812 1043-1802 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::07f3d4382695fc9f70d6aa9fb91b76a1 https://doi.org/10.1021/acs.bioconjchem.2c00115 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....07f3d4382695fc9f70d6aa9fb91b76a1 |
| قاعدة البيانات: | OpenAIRE |
Find this issue from the American Chemical Society | تدمد: | 15204812 10431802 |
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