Characterization of pleurocidin bioactive peptides

The zebrafish platform has been used to determine toxicity of all 26 pleurocidins in IMB's portfolio of bioactive peptides and indicated several cause developmental delays or defects that may be indicative of their role in disturbing specific cell-signalling pathways involved in cell death. Using more specific assays, we will focus on the role these pleurocidins play in promoting apoptosis for potential applications in cancer therapy and dissect the possible mechanism of action. Possible protein targets for pleurocidin binding will be investigated by Ebanks using biotinylated pleurocidin. We hope to enhance this research by building on the preliminary NMR-based metabolomic analysis of zebrafish being carried out by Karakach.  In addition, we will use microarray and/or qPCR technology to explore gene expression changes related to anti-cancer activity.

Some antimicrobial peptides also enhance wound-healing.  Based on the results of initial microarray studies with human cells, two pleurocidins appear to exhibit this activity. We will build on these results as well as those of INH collaborators (on mast cell degranulation and antiviral activities) to functionally characterize the role pleurocidins play in these important processes.

The specificity of pleurocidins for killing different kinds of cells will also be investigated by high resolution NMR using lipid bicelles that mimic different types of cell membranes (bacterial, eukaryotic, transformed) to determine structural attributes important for activity.  Additional structure-activity studies will involve the design and testing of peptide mimetics such as peptoids and peptides comprised of all D-amino acids.  Although these should be less susceptible to protease degradation, they may also have altered activity and so must be assayed to compare with their native homologs.

Related Information

Institutes:

• NRC Institute for Marine Biosciences