Peptide Array Based Discovery of Synthetic Antimicrobial Peptides

The rise of antibiotic resistance has emphasized the shortcomings in antibiotic drug development (Boucher et al., 2013). The move from biological based discovery methods to chemical approaches to identify candidates has left the antibiotic pipeline painfully dry (Lewis, 2013). The paucity of compounds that are effective against antibiotic resistant pathogens has led to great interest in antimicrobial peptides (AMPs) as potential solutions to the rise of resistant organisms (Hancock and Sahl, 2006; Fox, 2013). AMPs are short (5–50 amino acid) peptides that are produced by virtually all organisms as part of an innate immune system. There are 2,398 AMPs that have been reported (Antimicrobial Peptide Database—September 2013) and over 80% are cationic AMPs (CAMPs). Most positively charged AMPs interact with anionic bacterial membranes (Schmidtchen and Malmsten, 2013) which leads to a rapid breakdown in membrane function and subsequent cell death (Wimley, 2010). It is this mechanism of action that is of interest as it should be difficult for bacteria to develop resistance against lethal concentrations of CAMPs.