Antimicrobial activity of peptides derived from human ß-amyloid precursor protein.
(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:
https://lup.lub.lu.se/record/2336359
- author
- Papareddy, Praveen LU ; Mörgelin, Matthias LU ; Walse, Björn ; Schmidtchen, Artur LU and Malmsten, Martin LU
- organization
- publishing date
- 2012
- 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 Inc.
- external identifiers
-
- wos:000300710100006
- pmid:22249992
- scopus:84857507497
- pmid:22249992
- 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
- 2016-04-01 11:08:33
- date last changed
- 2022-02-03 00:10:00
@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}}, keywords = {{APP; antimicrobial; bacteria; liposomes; membrane; peptide}}, language = {{eng}}, number = {{3}}, pages = {{183--191}}, publisher = {{John Wiley & Sons Inc.}}, 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}}, doi = {{10.1002/psc.1439}}, volume = {{18}}, year = {{2012}}, }