High content analysis to determine cytotoxicity of the antimicrobial peptide, melittin and selected structural analogs

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dc.contributor.authorWalsh, Edwin G.-
dc.contributor.authorMaher, Sam-
dc.contributor.authorDevocelle, Marc-
dc.contributor.authorO'Brien, Peter J.-
dc.contributor.authorBaird, Alan W.-
dc.contributor.authorBrayden, David James-
dc.date.accessioned2011-07-14T14:44:36Z-
dc.date.available2011-07-14T14:44:36Z-
dc.date.copyright2011 Elsevier Inc.en
dc.date.issued2011-08-
dc.identifier.citationPeptidesen
dc.identifier.issn0196-9781-
dc.identifier.urihttp://hdl.handle.net/10197/3018-
dc.description.abstractAntimicrobial peptides (AMPs) are naturally occurring entities with potential as pharmaceutical candidates and/or food additives. They are present in many organisms including bacteria, insects, fish and mammals. While their antimicrobial activity is equipotent with many commercial antibiotics, current limitations are poor pharmacokinetics, stability and potential toxicology issues. Most elicit antimicrobial action via perturbation of bacterial membranes. Consequently, associated cytotoxicity in human cells is reflected by their capacity to lyse erythrocytes. However, more rigorous toxicological assessment of AMPs is required in order to predict potential failure at a later stage of development.Wedescribe a high-content analysis (HCA) screening protocol recently established for determination and prediction of safety in pharmaceutical drug discovery. HCA is a powerful, multi-parameter bioanalytical tool that amalgamates the actions of fluorescence microscopy with automated cell analysis software in order to understand multiple changes in cellular health. We describe the application of HCA in assessing cytotoxicity of the cytolytic-helical peptide, melittin, and selected structural analogs. The data shows that structural modification of melittin reduces its cytotoxic action and that HCA is suitable for rapidly identifying cytotoxicity.en
dc.description.sponsorshipScience Foundation Irelanden
dc.description.sponsorshipIrish Research Council for Science, Engineering and Technologyen
dc.description.sponsorshipOther funderen
dc.format.extent658617 bytes-
dc.format.mimetypeapplication/pdf-
dc.language.isoenen
dc.publisherElsevieren
dc.rightsAll rights reserved. This is the author’s version of a work that was accepted for publication in Peptides. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Peptides, DOI# 10.1016/j.peptides.2011.06.006 .en
dc.subjectHigh Content Analysisen
dc.subjectCytotoxicityen
dc.subjectPeptidesen
dc.subjectEpifluorescence microscopyen
dc.subject.lcshPeptide antibioticsen
dc.subject.lcshFluorescence microscopyen
dc.subject.lcshDrugs--Researchen
dc.subject.meshAntimicrobial Cationic Peptides--therapeutic useen
dc.subject.meshMicroscopy, Fluorescenceen
dc.subject.meshMelitten--therapeutic useen
dc.titleHigh content analysis to determine cytotoxicity of the antimicrobial peptide, melittin and selected structural analogsen
dc.typeJournal Articleen
dc.internal.availabilityFull text availableen
dc.internal.webversionshttp://dx.doi.org/10.1016/j.peptides.2011.06.006-
dc.statusPeer revieweden
dc.identifier.volume32en
dc.identifier.issue8en
dc.identifier.startpage1764en
dc.identifier.endpage1773en
dc.identifier.doi10.1016/j.peptides.2011.06.006-
dc.neeo.contributorWalsh|Edwin G.|aut|-
dc.neeo.contributorMaher|Sam|aut|-
dc.neeo.contributorDevocelle|Marc|aut|-
dc.neeo.contributorO'Brien|Peter J.|aut|-
dc.neeo.contributorBaird|Alan W.|aut|-
dc.neeo.contributorBrayden|David James|aut|-
dc.description.othersponsorshipMerrion Pharmaceuticalsen
dc.description.adminNYP: http://www.sciencedirect.com/science/article/pii/S0196978111002300 - AV 11/07/2011en
item.grantfulltextopen-
item.fulltextWith Fulltext-
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