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Boosting Antimicrobial Peptides by Hydrophobic Oligopeptide End Tags

Schmidtchen, Artur LU ; Pasupuleti, Mukesh LU ; Mörgelin, Matthias LU ; Davoudi, Mina LU ; Alenfall, Jan; Chalupka, Anna LU and Malmsten, Martin (2009) In Journal of Biological Chemistry 284(26). p.17584-17594
Abstract
A novel approach for boosting antimicrobial peptides through end tagging with hydrophobic oligopeptide stretches is demonstrated. Focusing on two peptides derived from kininogen, GKHKNKGKKNGKHNGWK (GKH17) and HKHGHGHGKHKNKGKKN (HKH17), tagging resulted in enhanced killing of Gram-positive Staphylococcus aureus, Gram-negative Escherichia coli, and fungal Candida albicans. Microbicidal potency increased with tag length, also in plasma, and was larger for Trp and Phe stretches than for aliphatic ones. The enhanced microbicidal effects correlated to a higher degree of bacterial wall rupture. Analogously, tagging promoted peptide binding to model phospholipid membranes and liposome rupture, particularly for anionic and cholesterol-void... (More)
A novel approach for boosting antimicrobial peptides through end tagging with hydrophobic oligopeptide stretches is demonstrated. Focusing on two peptides derived from kininogen, GKHKNKGKKNGKHNGWK (GKH17) and HKHGHGHGKHKNKGKKN (HKH17), tagging resulted in enhanced killing of Gram-positive Staphylococcus aureus, Gram-negative Escherichia coli, and fungal Candida albicans. Microbicidal potency increased with tag length, also in plasma, and was larger for Trp and Phe stretches than for aliphatic ones. The enhanced microbicidal effects correlated to a higher degree of bacterial wall rupture. Analogously, tagging promoted peptide binding to model phospholipid membranes and liposome rupture, particularly for anionic and cholesterol-void membranes. Tagged peptides displayed low toxicity, particularly in the presence of serum, and resisted degradation by human leukocyte elastase and by staphylococcal aureolysin and V8 proteinase. The biological relevance of these findings was demonstrated ex vivo and in vivo in porcine S. aureus skin infection models. The generality of end tagging for facile boosting of antimicrobial peptides without the need for post-synthesis modification was also demonstrated. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
284
issue
26
pages
17584 - 17594
publisher
ASBMB
external identifiers
  • wos:000267202500024
  • scopus:67650540782
ISSN
1083-351X
DOI
10.1074/jbc.M109.011650
language
English
LU publication?
yes
id
1bbd9d49-0b73-45dc-8d70-65d488fc7964 (old id 1441334)
date added to LUP
2009-07-28 10:22:46
date last changed
2017-10-22 03:40:50
@article{1bbd9d49-0b73-45dc-8d70-65d488fc7964,
  abstract     = {A novel approach for boosting antimicrobial peptides through end tagging with hydrophobic oligopeptide stretches is demonstrated. Focusing on two peptides derived from kininogen, GKHKNKGKKNGKHNGWK (GKH17) and HKHGHGHGKHKNKGKKN (HKH17), tagging resulted in enhanced killing of Gram-positive Staphylococcus aureus, Gram-negative Escherichia coli, and fungal Candida albicans. Microbicidal potency increased with tag length, also in plasma, and was larger for Trp and Phe stretches than for aliphatic ones. The enhanced microbicidal effects correlated to a higher degree of bacterial wall rupture. Analogously, tagging promoted peptide binding to model phospholipid membranes and liposome rupture, particularly for anionic and cholesterol-void membranes. Tagged peptides displayed low toxicity, particularly in the presence of serum, and resisted degradation by human leukocyte elastase and by staphylococcal aureolysin and V8 proteinase. The biological relevance of these findings was demonstrated ex vivo and in vivo in porcine S. aureus skin infection models. The generality of end tagging for facile boosting of antimicrobial peptides without the need for post-synthesis modification was also demonstrated.},
  author       = {Schmidtchen, Artur and Pasupuleti, Mukesh and Mörgelin, Matthias and Davoudi, Mina and Alenfall, Jan and Chalupka, Anna and Malmsten, Martin},
  issn         = {1083-351X},
  language     = {eng},
  number       = {26},
  pages        = {17584--17594},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {Boosting Antimicrobial Peptides by Hydrophobic Oligopeptide End Tags},
  url          = {http://dx.doi.org/10.1074/jbc.M109.011650},
  volume       = {284},
  year         = {2009},
}