Drug resistance is a major concern not only for antibiotic drugs but also for anticancer drugs. Instead of targeting specific proteins or signaling pathways, the disruption of the plasma membrane of microbial or cancer cells offers an opportunity for the discovery of new classes of antibacterial or anticancer agents. We present the biophysical characterization of lipid membrane-selective antimicrobial peptides (AMPs) and anticancer peptides (ACPs) [1]. For a deeper understanding of the processes involved we performed a comprehensive experimental study of the binding of natural and computer-generated AMPs and ACPs to lipid vesicles by nano isothermal titration calorimetry (ITC) and liquid nano differential scanning calorimetry (DSC). These investigations were complemented by observations made in other experiments e.g. membrane disruption assays and atomic force microscopy. The results show that membrane binding of the natural peptides is mostly entropy-driven, with only a small fraction of enthalpic contribution. Most of the designer peptides showed remarkably different thermal signatures, and a completely entropy driven process seems to facilitate binding or even the disruption of the membrane. [1] C. D. Fjell, J. A. Hiss, R. E. W. Hancock, G. Schneider, Nat. Rev. Drug Discov. 2012 , 11, 37-51.

Thermodynamic properties of membrane-binding peptides

248th National Meeting (2014)

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