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Importance of lipopolysaccharide aggregate disruption for the anti-endotoxic effects of heparin cofactor II peptides

Singh, Shalini; Papareddy, Praveen LU ; Kalle, Martina LU ; Schmidtchen, Artur LU and Malmsten, Martin (2013) In Biochimica et Biophysica Acta - Biomembranes 1828(11). p.2709-2719
Abstract
Lipid membrane and lipopolysaccharide (LPS) interactions were investigated for a series of amphiphilic and cationic peptides derived from human heparin cofactor II (HCII), using dual polarization interferometry, ellipsometry, circular dichroism (CD), cryoTEM, and z-potential measurements. Antimicrobial effects of these peptides were compared to their ability to disorder bacterial lipid membranes, while their capacity to block endotoxic effects of LPS was correlated to the binding of these peptides to LPS and its lipid A moiety, and to charge, secondary structure, and morphology of peptide/LPS complexes. While the peptide KYE28 (KYEITTIHNLERKLTHRLFRRNEGYTLR) displayed potent antimicrobial and anti-endotoxic effects, its truncated variants... (More)
Lipid membrane and lipopolysaccharide (LPS) interactions were investigated for a series of amphiphilic and cationic peptides derived from human heparin cofactor II (HCII), using dual polarization interferometry, ellipsometry, circular dichroism (CD), cryoTEM, and z-potential measurements. Antimicrobial effects of these peptides were compared to their ability to disorder bacterial lipid membranes, while their capacity to block endotoxic effects of LPS was correlated to the binding of these peptides to LPS and its lipid A moiety, and to charge, secondary structure, and morphology of peptide/LPS complexes. While the peptide KYE28 (KYEITTIHNLERKLTHRLFRRNEGYTLR) displayed potent antimicrobial and anti-endotoxic effects, its truncated variants KYE21 (KYEITTIHNLFRKLTHRLFRR) and NLF20 (NLFRKLTHRLFRRNFGYTLR) provide some clues on structure-activity relations, since KYE21 retains both the antimicrobial and anti-endotoxic effects of KYE28 (although both attenuated), while NLF20 retains the antimicrobial but only a fraction of the anti-endotoxic effect, hence locating the anti-endotoxic effects of KYE28 to its N-terminus. The antimicrobial effect, on the other hand, is primarily located at the C-terminus of KYE28. While displaying quite different endotoxic effects, these peptides bind to a similar extent to both LPS and lipid A, and also induce comparable LPS scavenging on model eukaryotic membranes. In contrast, fragmentation and densification of LPS aggregates, in turn dependent on the secondary structure in the peptide/LPS aggregates, correlate to the anti-endotoxic effect of these peptides, thus identifying peptide-induced packing transitions in LPS aggregates as key for anti-endotoxic functionality. This aspect therefore needs to be taken into account in the development of novel anti-endotoxic peptide therapeutics. (C) 2013 Published by Elsevier B.V. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Antimicrobial peptide, Dual polarization interferometry, Ellipsometry, Lipopolysaccharide, Liposome, Membrane
in
Biochimica et Biophysica Acta - Biomembranes
volume
1828
issue
11
pages
2709 - 2719
publisher
Elsevier
external identifiers
  • wos:000326143200038
  • scopus:84881512401
ISSN
0005-2736
DOI
10.1016/j.bbamem.2013.06.015
language
English
LU publication?
yes
id
1baf2de2-80e3-4836-b238-db7a37968e9e (old id 4212587)
date added to LUP
2014-01-03 10:47:26
date last changed
2019-06-19 02:20:27
@article{1baf2de2-80e3-4836-b238-db7a37968e9e,
  abstract     = {Lipid membrane and lipopolysaccharide (LPS) interactions were investigated for a series of amphiphilic and cationic peptides derived from human heparin cofactor II (HCII), using dual polarization interferometry, ellipsometry, circular dichroism (CD), cryoTEM, and z-potential measurements. Antimicrobial effects of these peptides were compared to their ability to disorder bacterial lipid membranes, while their capacity to block endotoxic effects of LPS was correlated to the binding of these peptides to LPS and its lipid A moiety, and to charge, secondary structure, and morphology of peptide/LPS complexes. While the peptide KYE28 (KYEITTIHNLERKLTHRLFRRNEGYTLR) displayed potent antimicrobial and anti-endotoxic effects, its truncated variants KYE21 (KYEITTIHNLFRKLTHRLFRR) and NLF20 (NLFRKLTHRLFRRNFGYTLR) provide some clues on structure-activity relations, since KYE21 retains both the antimicrobial and anti-endotoxic effects of KYE28 (although both attenuated), while NLF20 retains the antimicrobial but only a fraction of the anti-endotoxic effect, hence locating the anti-endotoxic effects of KYE28 to its N-terminus. The antimicrobial effect, on the other hand, is primarily located at the C-terminus of KYE28. While displaying quite different endotoxic effects, these peptides bind to a similar extent to both LPS and lipid A, and also induce comparable LPS scavenging on model eukaryotic membranes. In contrast, fragmentation and densification of LPS aggregates, in turn dependent on the secondary structure in the peptide/LPS aggregates, correlate to the anti-endotoxic effect of these peptides, thus identifying peptide-induced packing transitions in LPS aggregates as key for anti-endotoxic functionality. This aspect therefore needs to be taken into account in the development of novel anti-endotoxic peptide therapeutics. (C) 2013 Published by Elsevier B.V.},
  author       = {Singh, Shalini and Papareddy, Praveen and Kalle, Martina and Schmidtchen, Artur and Malmsten, Martin},
  issn         = {0005-2736},
  keyword      = {Antimicrobial peptide,Dual polarization interferometry,Ellipsometry,Lipopolysaccharide,Liposome,Membrane},
  language     = {eng},
  number       = {11},
  pages        = {2709--2719},
  publisher    = {Elsevier},
  series       = {Biochimica et Biophysica Acta - Biomembranes},
  title        = {Importance of lipopolysaccharide aggregate disruption for the anti-endotoxic effects of heparin cofactor II peptides},
  url          = {http://dx.doi.org/10.1016/j.bbamem.2013.06.015},
  volume       = {1828},
  year         = {2013},
}