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

Insight into mechanism of action and peptide-membrane interactions of Aib-rich peptides: multi-technique experimental and theoretical analysis
Insight into mechanism of action and peptide-membrane interactions of Aib-rich peptides: multi-technique experimental and theoretical analysis
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.
antimicrobial peptides, lipid peptide interaction, peptide partitioning, spectroscopy, transfer of chirality
1439-4227
1656-1667
Lizio, Maria Giovanna
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Campana, Mario
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De Poli, Matteo
fdfe6635-9622-4d9a-8396-25f0d7c79912
Jefferies, Damien Francis
8df97e21-8df6-4571-bfbe-3edc41e16967
Cullen, William
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Andrushchenko, Valery
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Chmel, Nikola P
e86d9ee1-3525-4aad-a939-0e47bddb731e
Bouř, Petr
173945fd-eb74-4ddf-a62d-a8396cc96798
Khalid, Syma
90fbd954-7248-4f47-9525-4d6af9636394
Clayden, Jonathan
a93f52e8-79f7-4ed8-93ba-68bcffb8e50a
Blanch, Ewan
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Rodger, Alison
a0db433a-17bd-474e-b349-49ef51c9e08c
Webb, Simon J
fb54d689-5045-4108-be42-c66e880410be
Lizio, Maria Giovanna
0c7719e4-49c4-4fcc-9c1f-b0b1e6c73cfe
Campana, Mario
d6dda54d-74e5-4946-b2fc-30bc1ffaebb8
De Poli, Matteo
fdfe6635-9622-4d9a-8396-25f0d7c79912
Jefferies, Damien Francis
8df97e21-8df6-4571-bfbe-3edc41e16967
Cullen, William
2b6da105-385e-430a-86e2-6f1597decb55
Andrushchenko, Valery
1bbe4719-cd2e-4528-9435-e933e2be6860
Chmel, Nikola P
e86d9ee1-3525-4aad-a939-0e47bddb731e
Bouř, Petr
173945fd-eb74-4ddf-a62d-a8396cc96798
Khalid, Syma
90fbd954-7248-4f47-9525-4d6af9636394
Clayden, Jonathan
a93f52e8-79f7-4ed8-93ba-68bcffb8e50a
Blanch, Ewan
5149101e-190e-4bf8-8bbb-509224713c7c
Rodger, Alison
a0db433a-17bd-474e-b349-49ef51c9e08c
Webb, Simon J
fb54d689-5045-4108-be42-c66e880410be

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

Record type: Article

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.

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Accepted/In Press date: 6 January 2021
e-pub ahead of print date: 7 January 2021
Keywords: antimicrobial peptides, lipid peptide interaction, peptide partitioning, spectroscopy, transfer of chirality

Identifiers

Local EPrints ID: 447066
URI: http://eprints.soton.ac.uk/id/eprint/447066
ISSN: 1439-4227
PURE UUID: d37341e2-f1ad-41b4-bc69-20c72bc557d0
ORCID for Syma Khalid: ORCID iD orcid.org/0000-0002-3694-5044

Catalogue record

Date deposited: 02 Mar 2021 17:32
Last modified: 22 Oct 2021 01:40

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Contributors

Author: Maria Giovanna Lizio
Author: Mario Campana
Author: Matteo De Poli
Author: Damien Francis Jefferies
Author: William Cullen
Author: Valery Andrushchenko
Author: Nikola P Chmel
Author: Petr Bouř
Author: Syma Khalid ORCID iD
Author: Jonathan Clayden
Author: Ewan Blanch
Author: Alison Rodger
Author: Simon J Webb

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