Magainin 2-PGLa Interactions in Membranes - Two Peptides that Exhibit Synergistic Enhancement of Antimicrobial Activity

Author(s): Arnaud Marquette , Evgeniy S. Salnikov , Elise Glattard , Christopher Aisenbrey , Burkhard Bechinger .

Journal Name: Current Topics in Medicinal Chemistry

Volume 16 , Issue 1 , 2016

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Graphical Abstract:


The structural requirements for the synergistic enhancement of antimicrobial activities of the cationic linear peptides PGLa and magainin 2 were investigated. In a first step the antimicrobial activities were evaluated for a number of modifications of the sequences and equimolar mixtures thereof. In particular fluorophore labelled peptides maintain a high degree of antimicrobial activity and considerable synergism when tested conjointly. Thereafter, circular dichroism spectroscopy indicated that these extended sequences adopt helical conformations in the presence of model membranes similar to the unmodified sequences. Energy transfer between the fluorophores suggested that the peptides reside in close proximity to each other when bound to the membrane surface at high concentrations. The fluorophore interactions quickly diminish at lower peptide-to-lipid ratios indicating that the peptide-peptide interactions are weak. Furthermore, 15N solid-state NMR measurements of the membrane topology of [15N-Ala14]-PGLa and of its fluorophorecarrying analogue reconstituted into supported 1, 2-didecanoyl-sn-glycero-3-phosphocholine bilayers were performed. These experiments revealed no correlation between the topological state of PGLa and the observed synergistic enhancement of antimicrobial activities due to the presence of magainins. These results suggest that lipid mediated interactions rather than the formation of tight peptide-peptide complexes in the membrane are responsible for synergistic activities of the mixtures.

Keywords: Amphipathic helix, Antimicrobial activities, FRET, Membrane topology, Peptide-lipid interactions, Solid-state NMR, Supported lipid bilayer.

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Article Details

Year: 2016
Page: [65 - 75]
Pages: 11
DOI: 10.2174/1568026615666150703115701

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