Background: Antimicrobial peptides (AMPs) from the skin secretions of amphibians are now considered as a potential alternative to conventional antibiotics. Phylloseptins are a family of AMPs identified in the skin secretions of Phyllomedusinae tree frogs which exhibit highly conserved structural characteristics. This study examines the structure–activity relationship of the newly discovered phylloseptin, Phylloseptin-PHa (PSPHa) from Pithecopus hypochondrialis . 
Materials and methods: PSPHa and modified analogs were produced by solid phase synthesis and purified by reverse-phase HPLC. Rationally designed modified analogs incorporating changes in significant physicochemical parameters such as hydrophobicity, hydrophobic moment and net charge were investigated to determine their influence on secondary structure, antimicrobial activity, membrane permeabilization and cytotoxicity. 
Results: Overall, we found that when rationally designing AMPs by altering their primary structure it is important to keep a balance between hydrophobicity and charge. 
Conclusion: This study provides new insights which will help in the future development of AMPs as alternatives to conventional antibiotics for the treatment of Staphylococcus aureus  and methicillin-resistant S. aureus  infections.
Keywords: phylloseptin, antimicrobial activity, hydrophobicity, charge, membrane selectivity