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

doi:10.1002/cbic.202000834

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

School of Chemistry

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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.

Original language	English
Pages (from-to)	1656-1667
Number of pages	12
Journal	ChemBioChem
Volume	22
Issue number	9
DOIs	https://doi.org/10.1002/cbic.202000834
Publication status	Published - 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

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Lizio, M. G., Campana, M., De Poli, M., Jefferies, D. F., Cullen, W., Andrushchenko, V., Chmel, N. P., Bouř, P., Khalid, S., Clayden, J., Blanch, E., Rodger, A., & Webb, S. J. (2021). Insight into the Mechanism of Action and Peptide-Membrane Interactions of Aib-Rich Peptides: Multitechnique Experimental and Theoretical Analysis. ChemBioChem, 22(9), 1656-1667. https://doi.org/10.1002/cbic.202000834

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title = "Insight into the Mechanism of Action and Peptide-Membrane Interactions of Aib-Rich Peptides: Multitechnique Experimental and Theoretical Analysis",

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.",

keywords = "antimicrobial peptides, lipid-peptide interactions, membranes, molecular dynamics, peptaibols, transfer of chirality",

author = "Lizio, {Maria Giovanna} and Mario Campana and {De Poli}, Matteo and Jefferies, {Damien F.} and William Cullen and Valery Andrushchenko and Chmel, {Nikola P.} and Petr Bou{\v r} and Syma Khalid and Jonathan Clayden and Ewan Blanch and Alison Rodger and Webb, {Simon J.}",

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: {\textcopyright} 2021 The Authors. ChemBioChem published by Wiley-VCH GmbH",

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Lizio, MG, Campana, M, De Poli, M, Jefferies, DF, Cullen, W, Andrushchenko, V, Chmel, NP, Bouř, P, Khalid, S, Clayden, J, Blanch, E, Rodger, A & Webb, SJ 2021, 'Insight into the Mechanism of Action and Peptide-Membrane Interactions of Aib-Rich Peptides: Multitechnique Experimental and Theoretical Analysis', ChemBioChem, vol. 22, no. 9, pp. 1656-1667. https://doi.org/10.1002/cbic.202000834

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T1 - Insight into the Mechanism of Action and Peptide-Membrane Interactions of Aib-Rich Peptides

T2 - Multitechnique Experimental and Theoretical Analysis

AU - Lizio, Maria Giovanna

AU - Campana, Mario

AU - De Poli, Matteo

AU - Jefferies, Damien F.

AU - Cullen, William

AU - Andrushchenko, Valery

AU - Chmel, Nikola P.

AU - Bouř, Petr

AU - Khalid, Syma

AU - Clayden, Jonathan

AU - Blanch, Ewan

AU - Rodger, Alison

AU - Webb, Simon J.

N1 - 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

PY - 2021/5/4

Y1 - 2021/5/4

N2 - 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.

AB - 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.

KW - antimicrobial peptides

KW - lipid-peptide interactions

KW - membranes

KW - molecular dynamics

KW - peptaibols

KW - transfer of chirality

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DO - 10.1002/cbic.202000834

M3 - Article (Academic Journal)

C2 - 33411956

AN - SCOPUS:85101328521

SN - 1439-4227

VL - 22

SP - 1656

EP - 1667

JO - ChemBioChem

JF - ChemBioChem

IS - 9

ER -

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

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Keywords

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