Stabilisation of mixed peptide/lipid complexes in selective antifungal hexapeptides

The design of antimicrobial peptides could have benefited from structural studies of known peptides having specific activity against target microbes, but not toward other microorganisms. We have previously reported the identification of a series of peptides (PAF-series) active against certain postharvest fungal phytopathogens, and devoid of toxicity towards E. coli and S. cerevisiae [López-García et al. Appl. Environ. Microbiol. 68 (2002) 2453]. The peptides inhibited the conidia germination and hyphal growth. Here, we present a comparative structural characterisation of selected PAF peptides obtained by single-amino-acid replacement, which differ in biological activity. The peptides were characterised in solution using fluorescence and circular dichroism (CD) spectroscopies. Membrane and membrane mimetic-peptide interactions and the lipid-bound structures were studied using fluorescence with the aid of extrinsic fluorescent probes that allowed the identification of mixed peptide/lipid complexes. A direct correlation was found between the capability of complex formation and antifungal activity. These studies provide a putative structural basis for the mechanism of action of selective antifungal peptides.