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Oligotryptophan-tagged antimicrobial peptides and the role of the cationic sequence

Stromstedt, Adam A.; Pasupuleti, Mukesh LU ; Schmidtchen, Artur LU and Malmsten, Martin (2009) In Biochimica et Biophysica Acta - Biomembranes 1788(9). p.1916-1923
Abstract
The effects of varying the cationic sequence of oligotryptophan-tagged antimicrobial peptides were investigated in terms of peptide adsorption to model lipid membranes, liposome leakage induction, and antibacterial potency. Heptamers of lysine (K7) and arginine (R7) were lytic against Escherichia coli bacteria at low ionic strength. In parallel, both peptides adsorbed on to bilayers formed by E. coli phospholipids, and caused leakage in the corresponding liposomes. K7 was the more potent of the two peptides in causing liposome leakage, although the adsorption of this peptide on E coli membranes was lower than that of R7. The bactericidal effect, liposome lysis, and membrane adsorption were all substantially reduced at physiological ionic... (More)
The effects of varying the cationic sequence of oligotryptophan-tagged antimicrobial peptides were investigated in terms of peptide adsorption to model lipid membranes, liposome leakage induction, and antibacterial potency. Heptamers of lysine (K7) and arginine (R7) were lytic against Escherichia coli bacteria at low ionic strength. In parallel, both peptides adsorbed on to bilayers formed by E. coli phospholipids, and caused leakage in the corresponding liposomes. K7 was the more potent of the two peptides in causing liposome leakage, although the adsorption of this peptide on E coli membranes was lower than that of R7. The bactericidal effect, liposome lysis, and membrane adsorption were all substantially reduced at physiological ionic strength. When a tryptophan pentamer tag was linked to the C-terminal end of these peptides, substantial peptide adsorption, membrane lysis, and bacterial killing were observed also at high ionic strength, and also for a peptide of lower cationic charge density (KNKGKKN-W5). Strikingly, the order of membrane lytic potential of the cationic peptides investigated was reversed when tagged. This and other aspects of peptide behavior and adsorption, in conjunction with effects on liposomes and bacteria, suggest that tagged and untagged peptides act by different lytic mechanisms, which to some extent counterbalance each other. Thus, while the untagged peptides act by generating negative curvature strain in the phospholipid membrane, the tagged peptides cause positive curvature strain. The tagged heptamer of arginine, R7W5, was the best candidate for E coli membrane lysis at physiological salt conditions and proved to be an efficient antibacterial agent. (C) 2009 Elsevier B.V. All rights reserved. (Less)
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organization
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type
Contribution to journal
publication status
published
subject
keywords
Oligoarginine, Oligolysine, Oligotryptophan, Ellipsometry, Bacteria, Liposome, Membrane, Bilayer, Phospholipid, End-tagged, Peptide, AMP, Antimicrobial
in
Biochimica et Biophysica Acta - Biomembranes
volume
1788
issue
9
pages
1916 - 1923
publisher
Elsevier
external identifiers
  • wos:000269859400025
  • scopus:68749107070
ISSN
0005-2736
DOI
10.1016/j.bbamem.2009.06.001
language
English
LU publication?
yes
id
3975c518-2544-4ca7-855c-40ac1ab65da2 (old id 1490783)
date added to LUP
2009-10-19 11:52:47
date last changed
2017-11-05 04:19:07
@article{3975c518-2544-4ca7-855c-40ac1ab65da2,
  abstract     = {The effects of varying the cationic sequence of oligotryptophan-tagged antimicrobial peptides were investigated in terms of peptide adsorption to model lipid membranes, liposome leakage induction, and antibacterial potency. Heptamers of lysine (K7) and arginine (R7) were lytic against Escherichia coli bacteria at low ionic strength. In parallel, both peptides adsorbed on to bilayers formed by E. coli phospholipids, and caused leakage in the corresponding liposomes. K7 was the more potent of the two peptides in causing liposome leakage, although the adsorption of this peptide on E coli membranes was lower than that of R7. The bactericidal effect, liposome lysis, and membrane adsorption were all substantially reduced at physiological ionic strength. When a tryptophan pentamer tag was linked to the C-terminal end of these peptides, substantial peptide adsorption, membrane lysis, and bacterial killing were observed also at high ionic strength, and also for a peptide of lower cationic charge density (KNKGKKN-W5). Strikingly, the order of membrane lytic potential of the cationic peptides investigated was reversed when tagged. This and other aspects of peptide behavior and adsorption, in conjunction with effects on liposomes and bacteria, suggest that tagged and untagged peptides act by different lytic mechanisms, which to some extent counterbalance each other. Thus, while the untagged peptides act by generating negative curvature strain in the phospholipid membrane, the tagged peptides cause positive curvature strain. The tagged heptamer of arginine, R7W5, was the best candidate for E coli membrane lysis at physiological salt conditions and proved to be an efficient antibacterial agent. (C) 2009 Elsevier B.V. All rights reserved.},
  author       = {Stromstedt, Adam A. and Pasupuleti, Mukesh and Schmidtchen, Artur and Malmsten, Martin},
  issn         = {0005-2736},
  keyword      = {Oligoarginine,Oligolysine,Oligotryptophan,Ellipsometry,Bacteria,Liposome,Membrane,Bilayer,Phospholipid,End-tagged,Peptide,AMP,Antimicrobial},
  language     = {eng},
  number       = {9},
  pages        = {1916--1923},
  publisher    = {Elsevier},
  series       = {Biochimica et Biophysica Acta - Biomembranes},
  title        = {Oligotryptophan-tagged antimicrobial peptides and the role of the cationic sequence},
  url          = {http://dx.doi.org/10.1016/j.bbamem.2009.06.001},
  volume       = {1788},
  year         = {2009},
}