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Tuning Liposome Membrane Permeability by Competitive Peptide Dimerization and Partitioning-Folding Interactions Regulated by Proteolytic Activity
Nanyang Technology University, Singapore.
Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
Nanyang Technology University, Singapore.
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2016 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, no 21123, 1-9 p.Article in journal (Refereed) PublishedText
Abstract [en]

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.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP , 2016. Vol. 6, no 21123, 1-9 p.
National Category
Physical Sciences Biochemistry and Molecular Biology
URN: urn:nbn:se:liu:diva-126131DOI: 10.1038/srep21123ISI: 000370532500002PubMedID: 26892926OAI: diva2:912071

Funding Agencies|Linkoping University; Swedish Research Council (VR); Swedish Foundation for Strategic Research (SSF); Knut and Alice Wallenberg Foundation (KAW); Centre in Nanoscience and Technology (CeNano); Provost Office, NTU

Available from: 2016-03-15 Created: 2016-03-15 Last updated: 2016-04-13

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