Insight into mechanism of action and peptide‐membrane interactions of Aib‐rich peptides: multi‐technique experimental and theoretical analysis

Maria Giovanna Lizio, Mario Campana, Matteo De Poli, Damien F. Jefferies, William Cullen, Valery Andrushchenko, Nikola P. Chmel, Petr Bouř, Syma Khalid, Jonathan Clayden, Ewan Blanch, Alison Rodger, Simon J. Webb

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Abstract

The increase in resistant bacterial strains necessitates the identification of new antimicrobial molecules. Antimicrobial peptides (AMPs) are an attractive option because of evidence that bacteria cannot easily develop resistance to AMPs. The peptaibols, a class of naturally‐occurring AMPs, have shown particular promise as antimicrobial drugs, but their development has been hindered because their mechanism of action is not clearly understood. To explore how peptaibols might interact with membranes, circular dichroism (CD), vibrational circular dichroism (VCD), linear dichroism (LD), Raman spectroscopy, Raman optical activity (ROA), neutron reflectivity and molecular dynamics simulations have been used to study a small library of peptaibol mimics, Aib‐rich peptides. All studied peptides quickly partitioned and oriented in membranes, and we found evidence of chiral interactions between the phospholipids and membrane‐embedded peptides. The protocols presented in this paper open new ground by showing how chiro‐optical spectroscopies can throw light on the mechanism of action of AMPs.
Original languageEnglish
JournalCHEMBIOCHEM
Early online date7 Jan 2021
DOIs
Publication statusPublished - 7 Jan 2021

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