title: 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 has been shown to be required for antimicrobial activity. However, whether this is a general requirement or whether C-terminal amidation is required for the anticancer activity of defence peptides is unclear. In response, this study analyses the toxicity of a series of C-terminally amidated defence peptides and their non-amidated isoforms to normal fibroblast cells, a variety of tumour cells and bacterial cells. The toxicities of these peptides to microbial and cancer cells were generally <200 microM. Peptides were either unaffected by C-terminal amidation or showed up to 10-fold decreases or increases in efficacy. However, these peptides all showed toxicity to normal fibroblast cells with levels (generally <150 microM) that were comparable to those of their antimicrobial and anticancer activities. In contrast to previous claims which have been based on analysis of single amidation events, the results of this study clearly show that the C-terminal amidation of defence peptides has a variable effect on their antimicrobial and anticancer efficacy and no clear effect on their selectivity for these cell types.
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, University of Central Lancashire, Preston, PR1 2HE, UK. srdennison1@uclan.ac.uk
authors.forename: Sarah Rachel
authors.initials: SR
authors.lastname: Dennison
authors.forename: Frederick
authors.initials: F
authors.lastname: Harris
authors.forename: Tailap
authors.initials: T
authors.lastname: Bhatt
authors.forename: Jaipaul
authors.initials: J
authors.lastname: Singh
authors.forename: David Andrew
authors.initials: DA
authors.lastname: Phoenix
mesh_terms: D000577:Amides / Q000737:chemistry*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D009369:Neoplasms / Q000188:drug therapy*
chemical_list: D000577:Amides; D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D000970:Antineoplastic Agents