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.
Bibliographical noteFunding 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).
© 2021 The Authors. ChemBioChem published by Wiley-VCH GmbH
- antimicrobial peptides
- lipid-peptide interactions
- molecular dynamics
- transfer of chirality