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Selectivity of Antimicrobial Peptides: A Complex Interplay of Multiple Equilibria

  • Sara Bobone
  • Lorenzo StellaEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1117)

Abstract

Antimicrobial peptides (AMPs) attack bacterial membranes selectively, killing microbes at concentrations that cause no toxicity to the host cells. This selectivity is not due to interaction with specific receptors but is determined by the different lipid compositions of the membranes of the two cell types and by the peculiar physicochemical properties of AMPs, particularly their cationic and amphipathic character. However, the available data, including recent studies of peptide-cell association, indicate that this picture is excessively simplistic, because selectivity is modulated by a complex interplay of several interconnected phenomena. For instance, conformational transitions and self-assembly equilibria modulate the effective peptide hydrophobicity, the electrostatic and hydrophobic contributions to the membrane-binding driving force are nonadditive, and kinetic processes can play an important role in selective bacterial killing in the presence of host cells. All these phenomena and their bearing on the final activity and toxicity of AMPs must be considered in the definition of design principles to optimize peptide selectivity.

Keywords

Antimicrobial peptides Host defense peptides Selectivity Toxicity Peptide-membrane association Aggregation Hydrophobicity Amphipathicity 

Notes

Acknowledgments

The authors gratefully thank Dr. F. Savini and Dr. A. Papi for their help with Figs. 11.3 and 11.5. Research in our lab is currently supported by the Italian Ministry for Education, University and Research (grant PRIN 20157WW5EH_007), and by the Italian Association for Cancer Research (AIRC grant IG 2016 19171).

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© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Department of Chemical Science and TechnologiesUniversity of Rome Tor VergataRomeItaly

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