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
LU
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1441334
- author
- Schmidtchen, Artur
LU
; Pasupuleti, Mukesh
LU
; Mörgelin, Matthias
LU
; Davoudi, Mina
LU
; Alenfall, Jan
; Chalupka, Anna
LU
and Malmsten, Martin
LU
- organization
- publishing date
- 2009
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Biological Chemistry
- volume
- 284
- issue
- 26
- pages
- 17584 - 17594
- publisher
- American Society for Biochemistry and Molecular Biology
- 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
- 2016-04-01 11:54:16
- date last changed
- 2022-04-20 23:30:58
@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 = {{American Society for Biochemistry and Molecular Biology}},
series = {{Journal of Biological Chemistry}},
title = {{Boosting Antimicrobial Peptides by Hydrophobic Oligopeptide End Tags}},
url = {{http://dx.doi.org/10.1074/jbc.M109.011650}},
doi = {{10.1074/jbc.M109.011650}},
volume = {{284}},
year = {{2009}},
}