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

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Author(s)
Walsh, Edwin G. 
Maher, Sam 
Devocelle, Marc 
O'Brien, Peter J. 
Baird, Alan W. 
Brayden, David James 
Uri
http://hdl.handle.net/10197/3018
Date Issued
August 2011
Date Available
14T14:44:36Z July 2011
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.
Sponsorship
Irish Research Council for Science, Engineering and Technology
Science Foundation Ireland
Other Sponsorship
Merrion Pharmaceuticals
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 Analysis...

  • Cytotoxicity

  • Peptides

  • Epifluorescence micro...

Subject – LCSH
Peptide antibiotics
Fluorescence microscopy
Drugs--Research
DOI
10.1016/j.peptides.2011.06.006
Web versions
http://dx.doi.org/10.1016/j.peptides.2011.06.006
Language
English
Status of Item
Peer reviewed
ISSN
0196-9781
This item is made available under a Creative Commons License
https://creativecommons.org/licenses/by-nc-sa/1.0/
Owning collection
Irish Drug Delivery Network Research Collection
Scopus© citations
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Mar 27, 2023
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