PEGylation enhances the antibacterial and therapeutic potential of amphibian host defence peptides.

Journal article

Dennison, S., Reddy, S.M., Morton, L.H.G., Harris, F., Badiani, K. and Phoenix, D.A (2021). PEGylation enhances the antibacterial and therapeutic potential of amphibian host defence peptides. Biochimica et biophysica acta. Biomembranes. 1864 (1), p. 183806. https://doi.org/10.1016/j.bbamem.2021.183806
AuthorsDennison, S., Reddy, S.M., Morton, L.H.G., Harris, F., Badiani, K. and Phoenix, D.A
AbstractAurein 2.1, aurein 2.6 and aurein 3.1 are amphibian host defence peptides that kill bacteria via the use of lytic amphiphilic α-helical structures. The C-terminal PEGylation of these peptides led to decreased antibacterial activity (Minimum Lethal Concentration (MLCs) ↓ circa one and a half to threefold), reduced levels of amphiphilic α-helical structure in solvents (α-helicity ↓ circa 15.0%) and lower surface activity (Δπ ↓ > 1.5 mN m ). This PEGylation of aureins also led to decreased levels of amphiphilic α-helical structure in the presence of anionic membranes and zwitterionic membranes (α-helicity↓ > 10.0%) as well as reduced levels of penetration (Δπ ↓ > 3.0 mN m ) and lysis (lysis ↓ > 10.0%) of these membranes. Based on these data, it was proposed that the antibacterial action of PEGylated aureins involved the adoption of α-helical structures that promote the lysis of bacterial membranes, but with lower efficacy than their native counterparts. However, PEGylation also reduced the haemolytic activity of native aureins to negligible levels (haemolysis ↓ from circa 10% to 3% or less) and improved their relative therapeutic indices (RTIs ↑ circa three to sixfold). Based on these data, it is proposed that PEGylated aureins possess the potential for therapeutic development; for example, to combat infections due to multi-drug resistant strains of S. aureus, designated as high priority by the World Health Organization. [Abstract copyright: Copyright © 2021 Elsevier B.V. All rights reserved.]
KeywordsLangmuir Blodgett monolayers; Aureins; Membrane interactions; α-Helical; Haemolysis; C-terminal PEGylation; Circular dichroism; Amphiphilic
Year2021
JournalBiochimica et biophysica acta. Biomembranes
Journal citation1864 (1), p. 183806
PublisherElsevier
ISSN1879-2642
Digital Object Identifier (DOI)https://doi.org/10.1016/j.bbamem.2021.183806
Publication dates
Online14 Oct 2021
Publication process dates
Accepted10 Oct 2021
Deposited24 Nov 2021
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