Development of Amphipathic Antimicrobial Peptide Foldamers Based on Magainin 2 Sequence

Magainin 2 (Mag 2), which is isolated from the skin of frogs, is a representative antimicrobial peptide (AMP), exerts its antimicrobial activity via microbial membrane disruption. It has been reported that both the amphipathicity and helical structure of Mag 2 play an important role in its antimicrobial activity. In this study, we revealed that the sequence of 17 amino acid residues in Mag 2 (peptide 7) is required to exert sufficient activity. We also designed a set of Mag 2 derivatives, based on enhancement of helicity and/or amphipathicity, by incorporation of α,α‐disubstituted amino acid residues into the Mag 2 fragment, and evaluated their preferred secondary structures and their antimicrobial activities against both Gram‐positive and Gram‐negative bacteria. As a result, peptide 11 formed a stable helical structure in solution, and possessed potent antimicrobial activities against both Gram‐positive and Gram‐negative bacteria without significant cytotoxicity. Antimicrobial peptide foldamers: We designed and synthesized amphipathic antimicrobial peptide foldamers based on the Magainin 2 sequence. In this study, we have revealed the 17‐residue sequence of Mag 2 (peptide 7) that is required to exert sufficient activity. We also designed a set of Mag 2 derivatives, based on the enhancement of helicity and/or amphipathicity, by incorporation of α,α‐disubstituted amino acids into the Mag 2 fragment, and evaluated their preferred secondary structures and their antimicrobial activities against both Gram‐positive and Gram‐negative bacteria.