The effect of C-terminal amidation on the efficacy and selectivity of antimicrobial and anticancer peptides

Abstract

Cationic defence peptides show high therapeutic potential as antimicrobial and anticancer agents. Some of these peptides carry a C-terminal amide moiety which appears to be required for antimicrobial activity. However, whether this is a general requirement and whether C-terminal amidtion is required for the anticancer activity of defence peptides is unclear. In reponse, we analyse the toxicity of a series of C-terminally amidated defence peptides and their non-amidated isoforms to normal fibrolast cells, a variety of tumour cells and bacterial cells. The toxicities of these peptides to microbial and cancer cells were generally < 200 μM and could either be unaffected by C-terminal amidation or show up to ten-fold decreases or increases. However, these peptides all showed toxcity to normal fibrolast cells with levels (generally < 150 μM) that were comparable to those of their antimicrobial and anticancer activities. In combination, these results clearly show that the C-terminal amidation of defence peptides has a variable effect on their antimicrobial and anticancer efficacy but no effect on their selectivity for these cell types.