Crown ether modified peptide interactions with model membranes^‡

ABSTRACT

A simple model of an uncharged antimicrobial peptide, carrying four crown ether side chains, is modified further by the selective incorporation of arginine side chains to control its secondary structure and its interaction with model membranes and living cells. Conformational studies show that shifting the position of a cationic residue in the peptide sequence allows to control its secondary structure and supramolecular self-assembly in solution. Results also demonstrate that the secondary structure influences the interaction with model membranes and cells. An α-helical peptide with greater amphiphilicity forms assemblies that interact with both prokaryotic and eukaryotic model membranes and cells. However, a β-stranded peptide with evenly distributed charges generates assemblies that interact more selectively with prokaryotic model membranes and cells. In addition, we observed differences in peptide orientation between uncharged and cationic α-helical peptides with different phospholipid bilayers. In general, the studied peptides have a higher affinity for thinner membranes, and cationic peptides interacted better with anionic membranes.

Graphical Abstract

KEYWORDS:

• Membrane active peptides
• crown ethers
• antimicrobial peptides
• oriented circular dichroism
• supramolecular assembly

Acknowledgments

This work was supported by the Natural Sciences and Engineering Research Council of Canada (NSERC), the Fonds de recherche du Québec-Nature et Technologies (FRQNT), and the Quebec Network for Research on Protein Function, Engineering, and Applications (PROTEO). P.-A.P.-C. acknowledges a graduate scholarship from FRQNT and from the CREATE Training Program in Bionanomachines (CTPB). P.-A. P.-C. also thanks the CTPB for an international fellowship. The authors thank Renée Bazin and Patrick Trépanier from Héma-Québec for their technical assistance with the haemolytic assay. We acknowledge the KIT light source for provision of instruments at the beamline UV-CD12 of the Institute of Biological Interfaces (IBG2) and we would like to thank the Institute for Beam Physics and Technology (IBPT) for the operation of the storage ring, the Karlsruhe Research Accelerator (KARA) and Bianca Posselt and Siegmar Roth for their assistance with the SR-OCD measurements.

Disclosure statement

No potential conflict of interest was reported by the authors.

Supplementary material

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Additional information

Funding

This work was supported by the Fonds de Recherche du Québec - Nature et Technologies (FRQNT) and the Natural Sciences and Engineering Research Council of Canada (NSERC) [RGPIN/04834-2017].