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
LU
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4212587
- author
- Singh, Shalini
; Papareddy, Praveen
LU
; Kalle, Martina
LU
; Schmidtchen, Artur
LU
and Malmsten, Martin
LU
- organization
- publishing date
- 2013
- 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
- pmid:23806651
- 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
- 2016-04-01 14:23:19
- date last changed
- 2022-01-28 00:24:07
@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}},
keywords = {{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}},
doi = {{10.1016/j.bbamem.2013.06.015}},
volume = {{1828}},
year = {{2013}},
}