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

Creator:

Walsh, Edwin G.; Maher, Sam; Devocelle, Marc; O'Brien, Peter J.; Baird, Alan W.; Brayden, David James;

Institution: Elsevier
Subject Keywords: High Content Analysis; Cytotoxicity; Peptides; Epifluorescence microscopy; Peptide antibiotics; Fluorescence microscopy; Drugs--Research; Antimicrobial Cationic Peptides--therapeutic use; Microscopy, Fluorescence; Melitten--therapeutic use;
Region:
Description:

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.

Format:

application/pdf

Related: http://dx.doi.org/10.1016/j.peptides.2011.06.006
Suggested citation:

Walsh, Edwin G.; Maher, Sam; Devocelle, Marc; O'Brien, Peter J.; Baird, Alan W.; Brayden, David James; . () High content analysis to determine cytotoxicity of the antimicrobial peptide, melittin and selected structural analogs [Online]. Available from: http://publichealthwell.ie/node/661402 [Accessed: 24th August 2019].

  

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