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Updated: Feb 24, 2026

In Vesiculo Synthesis of Peptide Membrane Precursors for Autonomous Vesicle Growth
Published on: June 28, 2019
Rational Design of Membrane-Pore-Forming Peptides
Max Pillong1, Jan A Hiss1, Petra Schneider1
1Department of Chemistry and Applied Biosciences, ETH Zurich, 8093, Zurich, Switzerland.
Abstract:
Specific interactions of peptides with lipid membranes are essential for cellular communication and constitute a central aspect of the innate host defense against pathogens. A computational method for generating innovative membrane-pore-forming peptides inspired by natural templates is presented. Peptide representation in terms of sequence- and topology-dependent hydrophobic moments is introduced. This design concept proves to be appropriate for the de novo generation of first-in-class membrane-active peptides with the anticipated mode of action. The designed peptides outperform the natural template in terms of their antibacterial activity. They form a kinked helical structure and self-assemble in the membrane by an entropy-driven mechanism to form dynamically growing pores that are dependent on the lipid composition. The results of this study demonstrate the unique potential of natural template-based peptide design for chemical biology and medicinal chemistry.
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