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Lipopolysaccharide Interactions of C-Terminal Peptides from Human Thrombin

Singh, Shalini; Kalle, Martina LU ; Papareddy, Praveen LU ; Schmidtchen, Artur LU and Malmsten, Martin (2013) In Biomacromolecules 14(5). p.1482-1492
Abstract
Interactions with bacterial lipopolysaccharide (LPS), both in aqueous solution and in lipid membranes, were investigated for a series of amphiphilic peptides derived from the C-terminal region of human thrombin, using ellipsometry, dual polarization interferometry, fluorescence spectroscopy, circular dichroism (CD), dynamic light scattering, and z-potential measurements. The ability of these peptides to block endotoxic effects caused by LPS, monitored through NO production in macrophages, was compared to peptide binding to LPS and its endotoxic component lipid A, and to size, charge, and secondary structure of peptide/LPS complexes. While the antiendotoxic peptide GKY25 (GKYGFYTHVFRL-KKWIQKVIDQFGE) displayed significant binding to both LPS... (More)
Interactions with bacterial lipopolysaccharide (LPS), both in aqueous solution and in lipid membranes, were investigated for a series of amphiphilic peptides derived from the C-terminal region of human thrombin, using ellipsometry, dual polarization interferometry, fluorescence spectroscopy, circular dichroism (CD), dynamic light scattering, and z-potential measurements. The ability of these peptides to block endotoxic effects caused by LPS, monitored through NO production in macrophages, was compared to peptide binding to LPS and its endotoxic component lipid A, and to size, charge, and secondary structure of peptide/LPS complexes. While the antiendotoxic peptide GKY25 (GKYGFYTHVFRL-KKWIQKVIDQFGE) displayed significant binding to both LPS and lipid A, so did two control peptides with either selected D-amino acid substitutions or with maintained composition but scrambled sequence, both displaying strongly attenuated antiendotoxic effects. Hence, the extent of LPS or lipid A binding is not the sole discriminant for the antiendotoxic effect of these peptides. In contrast, helix formation in peptide/LPS complexes correlates to the antiendotoxic effect of these peptides and is potentially linked to this functionality. Preferential binding to LPS over lipid membrane was furthermore demonstrated for these peptides and preferential binding to the lipid A moiety within LPS inferred. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Biomacromolecules
volume
14
issue
5
pages
1482 - 1492
publisher
The American Chemical Society
external identifiers
  • wos:000319034600027
  • scopus:84877742633
ISSN
1526-4602
DOI
10.1021/bm400150c
language
English
LU publication?
yes
id
8eac55c6-7b35-4970-a50c-ea959c7ab28a (old id 3932579)
date added to LUP
2013-07-15 10:58:49
date last changed
2019-02-20 02:51:44
@article{8eac55c6-7b35-4970-a50c-ea959c7ab28a,
  abstract     = {Interactions with bacterial lipopolysaccharide (LPS), both in aqueous solution and in lipid membranes, were investigated for a series of amphiphilic peptides derived from the C-terminal region of human thrombin, using ellipsometry, dual polarization interferometry, fluorescence spectroscopy, circular dichroism (CD), dynamic light scattering, and z-potential measurements. The ability of these peptides to block endotoxic effects caused by LPS, monitored through NO production in macrophages, was compared to peptide binding to LPS and its endotoxic component lipid A, and to size, charge, and secondary structure of peptide/LPS complexes. While the antiendotoxic peptide GKY25 (GKYGFYTHVFRL-KKWIQKVIDQFGE) displayed significant binding to both LPS and lipid A, so did two control peptides with either selected D-amino acid substitutions or with maintained composition but scrambled sequence, both displaying strongly attenuated antiendotoxic effects. Hence, the extent of LPS or lipid A binding is not the sole discriminant for the antiendotoxic effect of these peptides. In contrast, helix formation in peptide/LPS complexes correlates to the antiendotoxic effect of these peptides and is potentially linked to this functionality. Preferential binding to LPS over lipid membrane was furthermore demonstrated for these peptides and preferential binding to the lipid A moiety within LPS inferred.},
  author       = {Singh, Shalini and Kalle, Martina and Papareddy, Praveen and Schmidtchen, Artur and Malmsten, Martin},
  issn         = {1526-4602},
  language     = {eng},
  number       = {5},
  pages        = {1482--1492},
  publisher    = {The American Chemical Society},
  series       = {Biomacromolecules},
  title        = {Lipopolysaccharide Interactions of C-Terminal Peptides from Human Thrombin},
  url          = {http://dx.doi.org/10.1021/bm400150c},
  volume       = {14},
  year         = {2013},
}