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Structure–activity relationship of an antimicrobial peptide, Phylloseptin-PHa: balance of hydrophobicity and charge determines the selectivity of bioactivities

Authors Liu Y, Du Q, Ma C, Xi X, Wang L, Zhou M, Burrows JF, Chen T, Wang H

Received 16 October 2018

Accepted for publication 24 December 2018

Published 23 January 2019 Volume 2019:13 Pages 447—458

DOI https://doi.org/10.2147/DDDT.S191072

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Dr Tuo Deng


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


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