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Antimicrobial activity of peptides derived from human ß-amyloid precursor protein.

Papareddy, Praveen LU ; Mörgelin, Matthias LU ; Walse, Björn; Schmidtchen, Artur LU and Malmsten, Martin (2012) In Journal of Peptide Science 18(3). p.183-191
Abstract
Antimicrobial peptides are important effector molecules of the innate immune system. Here, we describe that peptides derived from the heparin-binding disulfide-constrained loop region of human ß-amyloid precursor protein are antimicrobial. The peptides investigated were linear and cyclic forms of NWCKRGRKQCKTHPH (NWC15) as well as the cyclic form comprising the C-terminal hydrophobic amino acid extension FVIPY (NWCKRGRKQCKTHPHFVIPY; NWC20c). Compared with the benchmark antimicrobial peptide LL-37, these peptides efficiently killed the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, the Gram-positive Staphylococcus aureus and Bacillus subtilis, and the fungi Candida albicans and Candida parapsilosis. Correspondingly,... (More)
Antimicrobial peptides are important effector molecules of the innate immune system. Here, we describe that peptides derived from the heparin-binding disulfide-constrained loop region of human ß-amyloid precursor protein are antimicrobial. The peptides investigated were linear and cyclic forms of NWCKRGRKQCKTHPH (NWC15) as well as the cyclic form comprising the C-terminal hydrophobic amino acid extension FVIPY (NWCKRGRKQCKTHPHFVIPY; NWC20c). Compared with the benchmark antimicrobial peptide LL-37, these peptides efficiently killed the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, the Gram-positive Staphylococcus aureus and Bacillus subtilis, and the fungi Candida albicans and Candida parapsilosis. Correspondingly, fluorescence and electron microscopy demonstrated that the peptides caused defects in bacterial membranes. Analogously, the peptides permeabilised negatively charged liposomes. Despite their bactericidal effect, the peptides displayed very limited hemolytic activities within the concentration range investigated and exerted very small membrane permeabilising effects on human epithelial cells. The efficiency of the peptides with respect to bacterial killing and liposome membrane leakage was in the order NWC20c > NWC15c > NWC15l, which also correlated to the adsorption density for these peptides at the model lipid membrane. Thus, whereas the cationic sequence is a minimum determinant for antimicrobial action, a constrained loop-structure as well as a hydrophobic extension further contributes to membrane permeabilising activity of this region of amyloid precursor protein. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
APP, antimicrobial, bacteria, liposomes, membrane, peptide
in
Journal of Peptide Science
volume
18
issue
3
pages
183 - 191
publisher
John Wiley & Sons
external identifiers
  • wos:000300710100006
  • pmid:22249992
  • scopus:84857507497
ISSN
1099-1387
DOI
10.1002/psc.1439
language
English
LU publication?
yes
id
3682dbef-2f1a-49ff-8c4c-3925a7a22607 (old id 2336359)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22249992?dopt=Abstract
date added to LUP
2012-02-01 21:36:51
date last changed
2017-10-01 03:30:57
@article{3682dbef-2f1a-49ff-8c4c-3925a7a22607,
  abstract     = {Antimicrobial peptides are important effector molecules of the innate immune system. Here, we describe that peptides derived from the heparin-binding disulfide-constrained loop region of human ß-amyloid precursor protein are antimicrobial. The peptides investigated were linear and cyclic forms of NWCKRGRKQCKTHPH (NWC15) as well as the cyclic form comprising the C-terminal hydrophobic amino acid extension FVIPY (NWCKRGRKQCKTHPHFVIPY; NWC20c). Compared with the benchmark antimicrobial peptide LL-37, these peptides efficiently killed the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, the Gram-positive Staphylococcus aureus and Bacillus subtilis, and the fungi Candida albicans and Candida parapsilosis. Correspondingly, fluorescence and electron microscopy demonstrated that the peptides caused defects in bacterial membranes. Analogously, the peptides permeabilised negatively charged liposomes. Despite their bactericidal effect, the peptides displayed very limited hemolytic activities within the concentration range investigated and exerted very small membrane permeabilising effects on human epithelial cells. The efficiency of the peptides with respect to bacterial killing and liposome membrane leakage was in the order NWC20c > NWC15c > NWC15l, which also correlated to the adsorption density for these peptides at the model lipid membrane. Thus, whereas the cationic sequence is a minimum determinant for antimicrobial action, a constrained loop-structure as well as a hydrophobic extension further contributes to membrane permeabilising activity of this region of amyloid precursor protein. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.},
  author       = {Papareddy, Praveen and Mörgelin, Matthias and Walse, Björn and Schmidtchen, Artur and Malmsten, Martin},
  issn         = {1099-1387},
  keyword      = {APP,antimicrobial,bacteria,liposomes,membrane,peptide},
  language     = {eng},
  number       = {3},
  pages        = {183--191},
  publisher    = {John Wiley & Sons},
  series       = {Journal of Peptide Science},
  title        = {Antimicrobial activity of peptides derived from human ß-amyloid precursor protein.},
  url          = {http://dx.doi.org/10.1002/psc.1439},
  volume       = {18},
  year         = {2012},
}