Destabilization of α-helical structure in solution improves bactericidal activity of antimicrobial peptides: Opposing effects on bacterial and viral targets

Ulaeto, David O., Morris, Christopher J., Fox, Marc A., Gumbleton, Mark and Beck, Konrad (2016) Destabilization of α-helical structure in solution improves bactericidal activity of antimicrobial peptides: Opposing effects on bacterial and viral targets. Antimicrobial Agents and Chemotherapy, 60 (4). pp. 1984-1991. ISSN 0066-4804

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Abstract

We have previously examined the mechanism of antimicrobial peptides on the outer membrane of vaccinia virus. Here we show that the formulation of peptides LL37 and magainin-2B amide in polysorbate 20 (Tween-20™) results in greater reductions in virus titre than formulation without detergent, and the effect is replicated by substitution of polysorbate 20 with high ionic strength buffer. In contrast, formulation with polysorbate 20 or high ionic strength buffer has the opposite effect on bactericidal activity of both peptides, resulting in lesser reductions in titre for both gram-positive and gram-negative bacteria. Circular dichroism spectroscopy shows that the differential action of polysorbate 20 and salt on the virucidal and bactericidal activities correlates with the α-helical content of peptide secondary structure in solution, suggesting that the virucidal and bactericidal activities are mediated through distinct mechanisms. The correlation of a defined structural feature with differential activity against a host-derived viral membrane and the membranes of both gram-positive and gram-negative bacteria suggests that overall helical content in solution under physiological conditions is an important feature for consideration in the design and development of candidate peptide-based antimicrobial compounds.

Item Type: Article
Additional Information: © Crown copyright 2016 This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
Faculty \ School: Faculty of Science > School of Pharmacy
Depositing User: Pure Connector
Date Deposited: 17 Feb 2016 17:00
Last Modified: 03 Sep 2020 23:41
URI: https://ueaeprints.uea.ac.uk/id/eprint/57158
DOI: 10.1128/AAC.02146-15

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