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Melittin peptides exhibit different activity on different cells and model membranes

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Abstract

Melittin (MLT) is a lytic peptide with a broad spectrum of activity against both eukaryotic and prokaryotic cells. To understand the role of proline and the thiol group of cysteine in the cytolytic activity of MLT, native MLT and cysteine-containing analogs were prepared using solid phase peptide synthesis. The antimicrobial and cytolytic activities of the monomeric and dimeric MLT peptides against different cells and model membranes were investigated. The results indicated that the proline residue was necessary for antimicrobial activity and cytotoxicity and its absence significantly reduced lysis of model membranes and hemolysis. Although lytic activity against model membranes decreased for the MLT dimer, hemolytic activity was increased. The native peptide and the MLT-P14C monomer were mainly unstructured in buffer while the dimer adopted a helical conformation. In the presence of neutral and negatively charged vesicles, the helical content of the three peptides was significantly increased. The lytic activity, therefore, is not correlated to the secondary structure of the peptides and, more particularly, on the propensity to adopt helical conformation.

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Acknowledgments

We acknowledge partial support of the studies undertaken in the authors’ laboratory by the Australian Research Council (DP150103522) to MAH and JDW. Research at the FNI was supported by the Victorian Government’s Operational Infrastructure Support Program. EJ thanks the University of Melbourne for an MIRS.

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The authors have no conflict of interest.

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Authors and Affiliations

  1. School of Chemistry, Bio21 Institute, University of Melbourne, Melbourne, VIC, 3010, Australia

    Elaheh Jamasbi, Marc-Antoine Sani, John D. Wade, Frances Separovic & Mohammed Akhter Hossain

  2. Department of Biochemistry and Molecular Biology, Bio21 Institute, University of Melbourne, Melbourne, VIC, 3010, Australia

    Steven Batinovic & Robyn A. Sharples

  3. Department of Microbiology and Immunology, Peter Doherty Institute, University of Melbourne, Melbourne, VIC, 3010, Australia

    Roy Michael Robins-Browne

  4. Murdoch Childrens Research Institute, Royal Children’s Hospital, Parkville, VIC, 3052, Australia

    Roy Michael Robins-Browne

  5. The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, VIC, 3010, Australia

    John D. Wade & Mohammed Akhter Hossain

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  1. Elaheh Jamasbi
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  2. Steven Batinovic
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Correspondence to Frances Separovic or Mohammed Akhter Hossain.

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Jamasbi, E., Batinovic, S., Sharples, R.A. et al. Melittin peptides exhibit different activity on different cells and model membranes. Amino Acids 46, 2759–2766 (2014). https://doi.org/10.1007/s00726-014-1833-9

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  • DOI: https://doi.org/10.1007/s00726-014-1833-9

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