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

Scientific Reports
Seng Koon LimDaniel Aili

Abstract

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.

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Citations

May 1, 2019·Advanced Biosystems·Federico Mazur, Rona Chandrawati
Dec 31, 2020·Advanced Drug Delivery Reviews·Johanna UtterströmDaniel Aili
Jan 20, 2021·Biochimica Et Biophysica Acta. Biomembranes·Brandt BertrandCarlos Munoz-Garay
May 15, 2018·Langmuir : the ACS Journal of Surfaces and Colloids·Camilla SkyttnerDaniel Aili

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Methods Mentioned

BETA
lipidation
transfection
circular dichroism
quartz crystal microbalance
gel filtration

Software Mentioned

QCM
ALV
CONTIN

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