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Effects of PEGylation on Membrane and Lipopolysaccharide Interactions of Host Defense Peptides

Singh, Shalini ; Papareddy, Praveen LU orcid ; Mörgelin, Matthias LU ; Schmidtchen, Artur LU and Malmsten, Martin LU (2014) In Biomacromolecules 15(4). p.1337-1345
Abstract
Effects of poly(ethylene glycol) (PEG) conjugation on peptide interactions with lipid membranes and lipopolysaccharide (LPS) were investigated for KYE28 (KYEITTIHNLFRKLTHRLFRRNFGYTLR), an antimicrobial and anti-inflammatory peptide derived from human heparin cofactor II. In particular, effects of PEG length and localization was investigated by ellipsometry, circular dichroism, nanoparticle tracking analysis, and fluorescence/electron microscopy. PEGylation of KYE28 reduces peptide binding to lipid membranes, an effect accentuated at increasing PEG length, but less sensitive to conjugation site. The reduced binding causes suppressed liposome leakage induction, as well as bacterial lysis. As a result of this, the antimicrobial effects of... (More)
Effects of poly(ethylene glycol) (PEG) conjugation on peptide interactions with lipid membranes and lipopolysaccharide (LPS) were investigated for KYE28 (KYEITTIHNLFRKLTHRLFRRNFGYTLR), an antimicrobial and anti-inflammatory peptide derived from human heparin cofactor II. In particular, effects of PEG length and localization was investigated by ellipsometry, circular dichroism, nanoparticle tracking analysis, and fluorescence/electron microscopy. PEGylation of KYE28 reduces peptide binding to lipid membranes, an effect accentuated at increasing PEG length, but less sensitive to conjugation site. The reduced binding causes suppressed liposome leakage induction, as well as bacterial lysis. As a result of this, the antimicrobial effects of KYE28 is partially lost with increasing PEG length, but hemolysis also strongly suppressed and selecticity improved. Through this, conditions can be found, at which the PEGylated peptide displays simultaneously efficient antimicrobial affects and low hemolysis in blood. Importantly, PEGylation does not markedly affect the anti-inflammatory effects of KYE28. The combination of reduced toxicity, increased selectivity, and retained anti-inflammatory effect after PEGylation, as well as reduced scavenging by serum proteins, thus shows that PEG conjugation may offer opportunities in the development of effective and selective anti-inflammatory peptides. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Biomacromolecules
volume
15
issue
4
pages
1337 - 1345
publisher
The American Chemical Society (ACS)
external identifiers
  • wos:000334571600026
  • scopus:84898652791
  • pmid:24588750
ISSN
1526-4602
DOI
10.1021/bm401884e
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Department of Dermatology and Venerology (013241320), Division of Infection Medicine (BMC) (013024020), Department of Dermatology and Venereology (Lund) (013006000)
id
5d0222ee-ed30-4e4e-af3e-6e46d42fe680 (old id 4488845)
date added to LUP
2016-04-01 11:00:55
date last changed
2021-09-01 04:06:23
@article{5d0222ee-ed30-4e4e-af3e-6e46d42fe680,
  abstract     = {Effects of poly(ethylene glycol) (PEG) conjugation on peptide interactions with lipid membranes and lipopolysaccharide (LPS) were investigated for KYE28 (KYEITTIHNLFRKLTHRLFRRNFGYTLR), an antimicrobial and anti-inflammatory peptide derived from human heparin cofactor II. In particular, effects of PEG length and localization was investigated by ellipsometry, circular dichroism, nanoparticle tracking analysis, and fluorescence/electron microscopy. PEGylation of KYE28 reduces peptide binding to lipid membranes, an effect accentuated at increasing PEG length, but less sensitive to conjugation site. The reduced binding causes suppressed liposome leakage induction, as well as bacterial lysis. As a result of this, the antimicrobial effects of KYE28 is partially lost with increasing PEG length, but hemolysis also strongly suppressed and selecticity improved. Through this, conditions can be found, at which the PEGylated peptide displays simultaneously efficient antimicrobial affects and low hemolysis in blood. Importantly, PEGylation does not markedly affect the anti-inflammatory effects of KYE28. The combination of reduced toxicity, increased selectivity, and retained anti-inflammatory effect after PEGylation, as well as reduced scavenging by serum proteins, thus shows that PEG conjugation may offer opportunities in the development of effective and selective anti-inflammatory peptides.},
  author       = {Singh, Shalini and Papareddy, Praveen and Mörgelin, Matthias and Schmidtchen, Artur and Malmsten, Martin},
  issn         = {1526-4602},
  language     = {eng},
  number       = {4},
  pages        = {1337--1345},
  publisher    = {The American Chemical Society (ACS)},
  series       = {Biomacromolecules},
  title        = {Effects of PEGylation on Membrane and Lipopolysaccharide Interactions of Host Defense Peptides},
  url          = {http://dx.doi.org/10.1021/bm401884e},
  doi          = {10.1021/bm401884e},
  volume       = {15},
  year         = {2014},
}