Tuning Liposome Membrane Permeability by Competitive Peptide Dimerization and Partitioning-Folding Interactions Regulated by Proteolytic Activity

Membrane active peptides are of large interest for development of drug delivery vehicles and therapeutics for treatment of multiple drug resistant infections. Lack of specificity can be detrimental and finding routes to tune specificity and activity of membrane active peptides is vital for improving...

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Bibliographic Details
Published in:Scientific reports 2016-02, Vol.6 (1), p.21123-21123, Article 21123
Main Authors: Lim, Seng Koon, Sandén, Camilla, Selegård, Robert, Liedberg, Bo, Aili, Daniel
Format: Article
Language:English
Subjects:
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Cell Membrane Permeability
Controlled release
Development strategies
Digestion
Dimerization
Drug delivery
Drug resistance
Drugs
Humanities and Social Sciences
Humans
Lipid Bilayers
Lipid membranes
Liposomes
Matrilysin
Matrix metalloproteinase
Membrane permeability
Membranes
Metalloproteinase
multidisciplinary
Multidrug resistance
Peptides
Peptides - chemistry
Peptides - metabolism
Permeability
Protein Folding
Protein Multimerization
Proteolysis
Science
Side effects
Tumors
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Summary:Membrane active peptides are of large interest for development of drug delivery vehicles and therapeutics for treatment of multiple drug resistant infections. Lack of specificity can be detrimental and finding routes to tune specificity and activity of membrane active peptides is vital for improving their therapeutic efficacy and minimize harmful side effects. We describe a de novo designed membrane active peptide that partition into lipid membranes only when specifically and covalently anchored to the membrane, resulting in pore-formation. Dimerization with a complementary peptide efficiently inhibits formation of pores. The effect can be regulated by proteolytic digestion of the inhibitory peptide by the matrix metalloproteinase MMP-7, an enzyme upregulated in many malignant tumors. This system thus provides a precise and specific route for tuning the permeability of lipid membranes and a novel strategy for development of recognition based membrane active peptides and indirect enzymatically controlled release of liposomal cargo.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep21123