A combinatorial approach to the discovery of biocidal six-residue cyclic D,L-α-peptides against the bacteria methicillin-resistant Staphylococcus aureus (MRSA) and E. coli and the biofouling algae Ulva linza and Navicula perminuta

James T. Fletcher, John A. Finlay, Maureen E. Callow, James A. Cailow, M. Reza Ghadiri

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Abstract

A combinatorial approach has been used to rapidly identify cyclic D,L-α-peptide hexamer sequences that exert biocidal activity towards both methicillin-resistant Staphylococcus aureus (MRSA) and E. coli bacteria, as well as the marine algae Ulva linza and Navicula perminuta. Evaluation of the effects against marine algae was facilitated by the development of a reliable, automated assay for toxicity, which should be of general utility for biofouling investigations. While the selective toxicity of cyclic D,L-α-peptides towards bacteria has been proven to be highly sensitive to minor changes in amino acid composition, this study demonstrates that this phenomenon extends to eukaryotic species as well, despite their significant structural differences. In performing toxicity assays on both prokaryotic and eukaryotic organisms in parallel, we have discovered examples of six-residue cyclic D,L-α-peptide sequences with either broad-spectrum or highly selective biocidal activities. Sequence [KWFFFH] (underlined amino acid abbreviations represent D-amino acid residues) was found to display 100-fold selectivity towards U. linza, demonstrating that the approach described herein may help lead to the development of new biofouling tools which are not generally toxic to all organisms, but rather specifically target microbial agents of interest.

Original languageEnglish
Pages (from-to)4008-4013
Number of pages6
JournalChemistry - A European Journal
Volume13
Issue number14
DOIs
StatePublished - 2007

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Biofouling
Methicillin
Algae
Escherichia coli
Peptides
Toxicity
Amino acids
Bacteria
Amino Acids
Assays
Poisons
Chemical analysis
peptide L

All Science Journal Classification (ASJC) codes

  • Chemistry(all)

Cite this

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abstract = "A combinatorial approach has been used to rapidly identify cyclic D,L-α-peptide hexamer sequences that exert biocidal activity towards both methicillin-resistant Staphylococcus aureus (MRSA) and E. coli bacteria, as well as the marine algae Ulva linza and Navicula perminuta. Evaluation of the effects against marine algae was facilitated by the development of a reliable, automated assay for toxicity, which should be of general utility for biofouling investigations. While the selective toxicity of cyclic D,L-α-peptides towards bacteria has been proven to be highly sensitive to minor changes in amino acid composition, this study demonstrates that this phenomenon extends to eukaryotic species as well, despite their significant structural differences. In performing toxicity assays on both prokaryotic and eukaryotic organisms in parallel, we have discovered examples of six-residue cyclic D,L-α-peptide sequences with either broad-spectrum or highly selective biocidal activities. Sequence [KWFFFH] (underlined amino acid abbreviations represent D-amino acid residues) was found to display 100-fold selectivity towards U. linza, demonstrating that the approach described herein may help lead to the development of new biofouling tools which are not generally toxic to all organisms, but rather specifically target microbial agents of interest.",
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AU - Fletcher, James T.

AU - Finlay, John A.

AU - Callow, Maureen E.

AU - Cailow, James A.

AU - Ghadiri, M. Reza

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