A Combinatorial Approach to the Discovery of Biocidal Six-Residue Cyclic D, L-α-Peptides Against Bacteria MRSA and E. coli. and the Biofouling Algae Ulva linza and Navicula perminuta

Abstract

A combinatorial approach has been used to rapidly identify cyclic D, L-α-peptide hexamer sequences that exert biocidal activity towards both 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 marine toxicity that 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 6-residue cyclic D, L-α-peptide sequences with either broad-spectrum or highly selective biocidal activities. Sequence [KWFFFH] 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 that are not generally toxic to all organisms, but rather specifically target microbial agents of interest.