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Membrane and lipopolysaccharide interactions of C-terminal peptides from S1 peptidases

Singh, Shalini; Kasetty, Gopinath LU ; Schmidtchen, Artur LU and Malmsten, Martin (2012) In Biochimica et Biophysica Acta - Biomembranes 1818(9). p.2244-2251
Abstract
The mechanisms underlying antimicrobial and anti-endotoxic effects were investigated for a series of structurally related peptides derived from the C-terminal region of S1 peptidases. For this purpose, results on bacterial killing were compared to those on peptide-induced liposome leakage, and to ellipsometry and dual polarization interferometry results on peptide binding to, and disordering of, supported lipid bilayers. Furthermore, the ability of these peptides to block endotoxic effects caused by bacterial lipopolysaccharide (LPS), monitored through NO production in macrophages, was compared to the binding of these peptides to LPS, and to secondary structure formation in the peptide/LPS complex. Bacteria killing, occurring through... (More)
The mechanisms underlying antimicrobial and anti-endotoxic effects were investigated for a series of structurally related peptides derived from the C-terminal region of S1 peptidases. For this purpose, results on bacterial killing were compared to those on peptide-induced liposome leakage, and to ellipsometry and dual polarization interferometry results on peptide binding to, and disordering of, supported lipid bilayers. Furthermore, the ability of these peptides to block endotoxic effects caused by bacterial lipopolysaccharide (LPS), monitored through NO production in macrophages, was compared to the binding of these peptides to LPS, and to secondary structure formation in the peptide/LPS complex. Bacteria killing, occurring through peptide-induced membrane lysis, was found to correlate with liposome rupture, and with the extent of peptide binding to the lipid membrane, no adsorption threshold for peptide insertion being observed. Membrane and LPS binding was found to depend on peptide net charge, illustrated by LPS binding increasing with increasing peptide charge, and peptides with net negative charge being unable to lyse membranes, kill bacteria, and block LPS-induced endotoxic effect. These effects were, however, also influenced by peptide hydrophobicity. LPS binding was furthermore demonstrated to be necessary, but not sufficient, for anti-endotoxic effect of these peptides. Circular dichroism spectroscopy showed that pronounced helix formation occurs in peptide/LPS complexes for all peptides displaying anti-endotoxic effect, hence potentially linked to this functionality. Similarly, ordered secondary structure formation was correlated to membrane binding, lysis, and antimicrobial activity of these peptides. Finally, preferential binding of these peptides to LPS over the lipid membrane was demonstrated. (C) 2012 Elsevier B.V. All rights reserved. (Less)
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author
organization
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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
1818
issue
9
pages
2244 - 2251
publisher
Elsevier
external identifiers
  • wos:000306882600019
  • scopus:84861813332
ISSN
0005-2736
DOI
10.1016/j.bbamem.2012.03.017
language
English
LU publication?
yes
id
452be1f6-7721-46be-949b-2809023ace2d (old id 3073554)
date added to LUP
2012-10-05 07:14:14
date last changed
2017-10-22 04:08:47
@article{452be1f6-7721-46be-949b-2809023ace2d,
  abstract     = {The mechanisms underlying antimicrobial and anti-endotoxic effects were investigated for a series of structurally related peptides derived from the C-terminal region of S1 peptidases. For this purpose, results on bacterial killing were compared to those on peptide-induced liposome leakage, and to ellipsometry and dual polarization interferometry results on peptide binding to, and disordering of, supported lipid bilayers. Furthermore, the ability of these peptides to block endotoxic effects caused by bacterial lipopolysaccharide (LPS), monitored through NO production in macrophages, was compared to the binding of these peptides to LPS, and to secondary structure formation in the peptide/LPS complex. Bacteria killing, occurring through peptide-induced membrane lysis, was found to correlate with liposome rupture, and with the extent of peptide binding to the lipid membrane, no adsorption threshold for peptide insertion being observed. Membrane and LPS binding was found to depend on peptide net charge, illustrated by LPS binding increasing with increasing peptide charge, and peptides with net negative charge being unable to lyse membranes, kill bacteria, and block LPS-induced endotoxic effect. These effects were, however, also influenced by peptide hydrophobicity. LPS binding was furthermore demonstrated to be necessary, but not sufficient, for anti-endotoxic effect of these peptides. Circular dichroism spectroscopy showed that pronounced helix formation occurs in peptide/LPS complexes for all peptides displaying anti-endotoxic effect, hence potentially linked to this functionality. Similarly, ordered secondary structure formation was correlated to membrane binding, lysis, and antimicrobial activity of these peptides. Finally, preferential binding of these peptides to LPS over the lipid membrane was demonstrated. (C) 2012 Elsevier B.V. All rights reserved.},
  author       = {Singh, Shalini and Kasetty, Gopinath and Schmidtchen, Artur and Malmsten, Martin},
  issn         = {0005-2736},
  keyword      = {Antimicrobial peptide,Dual polarization interferometry,Ellipsometry,Lipopolysaccharide,Liposome,Membrane},
  language     = {eng},
  number       = {9},
  pages        = {2244--2251},
  publisher    = {Elsevier},
  series       = {Biochimica et Biophysica Acta - Biomembranes},
  title        = {Membrane and lipopolysaccharide interactions of C-terminal peptides from S1 peptidases},
  url          = {http://dx.doi.org/10.1016/j.bbamem.2012.03.017},
  volume       = {1818},
  year         = {2012},
}