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

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Title: High content analysis to determine cytotoxicity of the antimicrobial peptide, melittin and selected structural analogs
Authors: Walsh, Edwin G.
Maher, Sam
Devocelle, Marc
O'Brien, Peter J.
Baird, Alan W.
Brayden, David James
Permanent link: http://hdl.handle.net/10197/3018
Date: Aug-2011
Online since: 2011-07-14T14:44:36Z
Abstract: Antimicrobial 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.
Funding Details: Science Foundation Ireland
Irish Research Council for Science, Engineering and Technology
Other funder
Type of material: Journal Article
Publisher: Elsevier
Journal: Peptides
Volume: 32
Issue: 8
Start page: 1764
End page: 1773
Copyright (published version): 2011 Elsevier Inc.
Keywords: High Content AnalysisCytotoxicityPeptidesEpifluorescence microscopy
Subject LCSH: Peptide antibiotics
Fluorescence microscopy
DOI: 10.1016/j.peptides.2011.06.006
Other versions: http://dx.doi.org/10.1016/j.peptides.2011.06.006
Language: en
Status of Item: Peer reviewed
Appears in Collections:Irish Drug Delivery Network Research Collection

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