Antimicrobial properties of analgesic kyotorphin peptides unraveled through atomic force microscopy
dc.contributor.author
dc.date.accessioned
2015-03-23T11:08:43Z
dc.date.available
2015-03-23T11:08:43Z
dc.date.issued
2012-04-13
dc.identifier.issn
0006-291X
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dc.description.abstract
Antimicrobial peptides (AMPs) are promising candidates as alternatives to conventional antibiotics for the treatment of resistant pathogens. In the last decades, new AMPs have been found from the cleavage of intact proteins with no antibacterial activity themselves. Bovine hemoglobin hydrolysis, for instance, results in AMPs and the minimal antimicrobial peptide sequence was defined as Tyr-Arg plus a positively charged amino acid residue. The Tyr-Arg dipeptide alone, known as kyotorphin (KTP), is an endogenous analgesic neuropeptide but has no antimicrobial activity itself. In previous studies new KTP derivatives combining C-terminal amidation and Ibuprofen (Ib) - KTP-NH 2, IbKTP, IbKTP-NH 2 - were designed in order to improve KTP brain targeting. Those modifications succeeded in enhancing peptide-cell membrane affinity towards fluid anionic lipids and higher analgesic activity after systemic injection resulted therefrom. Here, we investigated if this affinity for anionic lipid membranes also translates into antimicrobial activity because bacteria have anionic membranes. Atomic force microscopy revealed that KTP derivatives perturbed Staphylococcus aureus membrane structure by inducing membrane blebbing, disruption and lysis. In addition, these peptides bind to red blood cells but are non-hemolytic. From the KTP derivatives tested, amidated KTP proves to be the most active antibacterial agent. The combination of analgesia and antibacterial activities with absence of toxicity is highly appealing from the clinical point of view and broadens the therapeutic potential and application of kyotorphin peptides
dc.description.sponsorship
Unidade de Microbiologia Molecular e Infeccao from Instituto de Medicina Molecular are acknowledged for the kind gift of E. coli and S. aureus strains. Dr. Sonia T. Henriques is acknowledged for helpful discussions. Fundacao para a Ciencia e Tecnologia (Portugal) is acknowledged for funding (SFRH/BD/42158/2007 fellowship to M.M.B.R. and SFRH/BD/39039/2007 fellowship to H.G.F.). Marie Curie Industry-Academia Partnerships and Pathways (European Commission) is also acknowledged for funding and fellowship to V. G. R. (FP7-PEOPLE-2007-3-1-IAPP, Project 230654)
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application/pdf
dc.language.iso
eng
dc.publisher
Elsevier
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Reproducció digital del document publicat a: http://dx.doi.org/10.1016/j.bbrc.2012.03.065
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© Biochemical and Biophysical Research Communications, 2012, vol. 420, p. 676-679
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Articles publicats (D-Q)
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Tots els drets reservats
dc.subject
dc.title
Antimicrobial properties of analgesic kyotorphin peptides unraveled through atomic force microscopy
dc.type
info:eu-repo/semantics/article
dc.rights.accessRights
info:eu-repo/semantics/embargoedAccess
dc.embargo.terms
Cap
dc.date.embargoEndDate
info:eu-repo/date/embargoEnd/2026-01-01
dc.relation.projectID
info:eu-repo/grantAgreement/EC/FP7/230654/EU/Selected peptides as drug candidates directed to pain and neurodegeneration/PEP2BRAIN
dc.type.version
info:eu-repo/semantics/publishedVersion
dc.identifier.doi
dc.identifier.idgrec
021455
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dc.relation.ProjectAcronym