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Peptide-Folding Tri...
Peptide-Folding Triggered Phase Separation and Lipid Membrane Destabilization in Cholesterol-Rich Lipid Vesicles
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- Utterström, Johanna (författare)
- Linköpings universitet,Biofysik och bioteknik,Tekniska fakulteten
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- Barriga, Hanna M. G. (författare)
- Karolinska Institutet,Karolinska Inst, Sweden
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- Holme, Margaret N. (författare)
- Karolinska Institutet,Karolinska Inst, Sweden
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- Selegård, Robert (författare)
- Linköpings universitet,Biofysik och bioteknik,Tekniska fakulteten
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- Stevens, Molly M. (författare)
- Karolinska Institutet,Karolinska Inst, Sweden; Imperial Coll London, England; Imperial Coll London, England
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- Aili, Daniel (författare)
- Linköpings universitet,Biofysik och bioteknik,Tekniska fakulteten
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(creator_code:org_t)
- 2022-04-01
- 2022
- Engelska.
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Ingår i: Bioconjugate chemistry. - : AMER CHEMICAL SOC. - 1043-1802 .- 1520-4812. ; 33:4, s. 736-746
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Läkemedelskemi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medicinal Chemistry (hsv//eng)
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