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Effects of single amino acid substitutions on peptide interaction with lipid membranes and bacteria-variants of GKE21, an internal sequence from human LL-37

Ringstad, Lovisa; Schmidtchen, Artur LU and Malmsten, Martin (2010) In Colloids and Surfaces A: Physicochemical and Engineering Aspects 354(1-3). p.65-71
Abstract
Effects of helix destabilization on lipid membrane interaction, liposome rupture, and bacterial killing was investigated for variants of the antimicrobial peptide GKE21 (GKEFKRIVQRIKDFLRNLVPR), an internal sequence of human cathelicidin LL-37, by ellipsometry, circular dichroism, fluorescence spectroscopy, and bacterial radial diffusion assay. GKE21 displayed moderate helix induction in buffer, which increased on interaction with phospholipid membranes. Substituting either of the two valines (V) in GKE21 with either proline (P) or D-valine (dV) resulted in helix destabilization, while peptide isoelectric point, net charge at pH 7.4, and mean hydrophobicity remained unchanged. The decreased tendency for helix formation in GKE21 (V -> P,... (More)
Effects of helix destabilization on lipid membrane interaction, liposome rupture, and bacterial killing was investigated for variants of the antimicrobial peptide GKE21 (GKEFKRIVQRIKDFLRNLVPR), an internal sequence of human cathelicidin LL-37, by ellipsometry, circular dichroism, fluorescence spectroscopy, and bacterial radial diffusion assay. GKE21 displayed moderate helix induction in buffer, which increased on interaction with phospholipid membranes. Substituting either of the two valines (V) in GKE21 with either proline (P) or D-valine (dV) resulted in helix destabilization, while peptide isoelectric point, net charge at pH 7.4, and mean hydrophobicity remained unchanged. The decreased tendency for helix formation in GKE21 (V -> P, V -> dV) resulted in a lower induced (helix-related) amphiphilicity, and correlated to a lower peptide adsorption at supported phospholipid membranes, as well as to decreased peptide-induced liposome leakage, particularly at high electrolyte concentration where conformation-invariant electrostatic interactions are screened. In addition, bacterial killing was reduced for the substituted peptides, indicating that even minor changes in induced peptide amphiphilicity may be of relevance for the bactericidal properties of this type of antimicrobial peptides. (C) 2009 Elsevier B.V. All rights reserved. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
LL-37, Liposome, Ellipsometry, AMP, Antimicrobial peptide
in
Colloids and Surfaces A: Physicochemical and Engineering Aspects
volume
354
issue
1-3
pages
65 - 71
publisher
Elsevier
external identifiers
  • wos:000275351300012
  • scopus:73049084108
ISSN
0927-7757
DOI
10.1016/j.colsurfa.2009.04.018
language
English
LU publication?
yes
id
12ab8e72-818b-40c4-a3d3-d7d531b5d1bd (old id 1589106)
date added to LUP
2010-04-20 13:37:28
date last changed
2018-06-24 04:20:23
@article{12ab8e72-818b-40c4-a3d3-d7d531b5d1bd,
  abstract     = {Effects of helix destabilization on lipid membrane interaction, liposome rupture, and bacterial killing was investigated for variants of the antimicrobial peptide GKE21 (GKEFKRIVQRIKDFLRNLVPR), an internal sequence of human cathelicidin LL-37, by ellipsometry, circular dichroism, fluorescence spectroscopy, and bacterial radial diffusion assay. GKE21 displayed moderate helix induction in buffer, which increased on interaction with phospholipid membranes. Substituting either of the two valines (V) in GKE21 with either proline (P) or D-valine (dV) resulted in helix destabilization, while peptide isoelectric point, net charge at pH 7.4, and mean hydrophobicity remained unchanged. The decreased tendency for helix formation in GKE21 (V -> P, V -> dV) resulted in a lower induced (helix-related) amphiphilicity, and correlated to a lower peptide adsorption at supported phospholipid membranes, as well as to decreased peptide-induced liposome leakage, particularly at high electrolyte concentration where conformation-invariant electrostatic interactions are screened. In addition, bacterial killing was reduced for the substituted peptides, indicating that even minor changes in induced peptide amphiphilicity may be of relevance for the bactericidal properties of this type of antimicrobial peptides. (C) 2009 Elsevier B.V. All rights reserved.},
  author       = {Ringstad, Lovisa and Schmidtchen, Artur and Malmsten, Martin},
  issn         = {0927-7757},
  keyword      = {LL-37,Liposome,Ellipsometry,AMP,Antimicrobial peptide},
  language     = {eng},
  number       = {1-3},
  pages        = {65--71},
  publisher    = {Elsevier},
  series       = {Colloids and Surfaces A: Physicochemical and Engineering Aspects},
  title        = {Effects of single amino acid substitutions on peptide interaction with lipid membranes and bacteria-variants of GKE21, an internal sequence from human LL-37},
  url          = {http://dx.doi.org/10.1016/j.colsurfa.2009.04.018},
  volume       = {354},
  year         = {2010},
}