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

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Lizio, Maria Giovanna, Campana, Mario, De Poli, Matteo, Jefferies, Damien F., Cullen, William, Andrushchenko, Valery, Chmel, Nikola Paul, Bouř, Petr, Khalid, Syma, Clayden, Jonathan, Blanch, Ewan, Rodger, Alison and Webb, Simon J. (2021) Insight into the mechanism of action and peptide‐membrane interactions of Aib‐rich peptides : multitechnique experimental and theoretical analysis. Chembiochem, 22 (9). pp. 1656-1667. doi:10.1002/cbic.202000834 ISSN 1439-4227.

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Official URL: https://doi.org/10.1002/cbic.202000834

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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 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.

Item Type: Journal Article
Subjects: Q Science > QH Natural history
Q Science > QR Microbiology
R Medicine > RS Pharmacy and materia medica
Divisions: Faculty of Science, Engineering and Medicine > Science > Chemistry
SWORD Depositor: Library Publications Router
Library of Congress Subject Headings (LCSH): Peptide antibiotics, Cells -- Permeability, Bilayer lipid membranes -- Permeability, Drug resistance in microorganisms
Journal or Publication Title: Chembiochem
Publisher: Wiley
ISSN: 1439-4227
Official Date: May 2021
Dates:
DateEvent
May 2021Published
7 January 2021Available
7 January 2021Accepted
Volume: 22
Number: 9
Page Range: pp. 1656-1667
DOI: 10.1002/cbic.202000834
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access (Creative Commons)
Date of first compliant deposit: 23 February 2022
Date of first compliant Open Access: 23 February 2022
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
1600026[STFC] Science and Technology Facilities Councilhttp://dx.doi.org/10.13039/501100000271
1910639[STFC] Science and Technology Facilities Councilhttp://dx.doi.org/10.13039/501100000271
EP/P027067/1[EPSRC] Engineering and Physical Sciences Research Councilhttp://dx.doi.org/10.13039/501100000266
EP/N009134/1[EPSRC] Engineering and Physical Sciences Research Councilhttp://dx.doi.org/10.13039/501100000266
CZ.02.1.01/0.0/0.0/16_019/0000729[ERDF] European Regional Development Fundhttp://dx.doi.org/10.13039/501100008530
ROCOCOEuropean Research Councilhttp://dx.doi.org/10.13039/501100000781
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