Insight into the Mechanism of Action and Peptide-Membrane Interactions of Aib-Rich Peptides: Multitechnique 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

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

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 by their mechanism of action not being clearly understood. To explore how peptaibols might interact with membranes, circular dichroism, vibrational circular dichroism, linear dichroism, Raman spectroscopy, Raman optical activity, neutron reflectivity and molecular dynamics simulations have been used to study a small library of peptaibol mimics, the Aib-rich peptides. All the peptides studied 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
Pages (from-to)1656-1667
Number of pages12
JournalChemBioChem
Volume22
Issue number9
DOIs
Publication statusPublished - 4 May 2021

Bibliographical note

Funding Information:
M.L., M.C. and S.J.W. would like to thank the STFC Rutherford Appleton Laboratory for funding time on SURF (ref. no. 1600026) and INTER (ref. no. 1910639) at the ISIS Neutron and Muon Source. S.J.W. and W.C. would like to thank the EPSRC (grants EP/P027067/1 and EP/N009134/1) for support. V.A. and P.B. thank the Czech Ministry of Education (grant CZ.02.1.01/0.0/0.0/16_019/0000729) for support. M.D.P. and J.C. would like to thank the European Research Council (Advanced Investigator Grant ROCOCO).

Publisher Copyright:
© 2021 The Authors. ChemBioChem published by Wiley-VCH GmbH

Keywords

  • antimicrobial peptides
  • lipid-peptide interactions
  • membranes
  • molecular dynamics
  • peptaibols
  • transfer of chirality

Fingerprint

Dive into the research topics of 'Insight into the Mechanism of Action and Peptide-Membrane Interactions of Aib-Rich Peptides: Multitechnique Experimental and Theoretical Analysis'. Together they form a unique fingerprint.

Cite this