Drug Design, Development and Therapy (Jan 2019)
Structure–activity relationship of an antimicrobial peptide, Phylloseptin-PHa: balance of hydrophobicity and charge determines the selectivity of bioactivities
Abstract
Yuzhang Liu,1,2,* Qiang Du,1,* Chengbang Ma,2 Xinping Xi,2 Lei Wang,2 Mei Zhou,2 James F Burrows,2 Tianbao Chen,2 Hui Wang1 1School of Pharmacy, China Medical University, Shenyang 110001, Liaoning, China; 2Faculty of Medicine, Health and Life Sciences, School of Pharmacy, Queen’s University Belfast, Belfast BT9 7BL, Northern Ireland, UK *These authors contributed equally to this work 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
