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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

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
2011-08
Date Available
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.
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.
Subjects

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/
File(s)
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Size

643.18 KB

Format

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Checksum (MD5)

5798bffd3f30ff219a9d8f30b2698608

Owning collection
Irish Drug Delivery Network Research Collection

Item descriptive metadata is released under a CC-0 (public domain) license: https://creativecommons.org/public-domain/cc0/.
All other content is subject to copyright.

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