Amino Acids

, Volume 46, Issue 12, pp 2759–2766 | Cite as

Melittin peptides exhibit different activity on different cells and model membranes

  • Elaheh Jamasbi
  • Steven Batinovic
  • Robyn A. Sharples
  • Marc-Antoine Sani
  • Roy Michael Robins-Browne
  • John D. Wade
  • Frances Separovic
  • Mohammed Akhter Hossain
Original Article


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.


Melittin Antimicrobial peptide Cytotoxicity Hemolysis Dye leakage 



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.

Conflict of interest

The authors have no conflict of interest.


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Copyright information

© Springer-Verlag Wien 2014

Authors and Affiliations

  • Elaheh Jamasbi
    • 1
  • Steven Batinovic
    • 2
  • Robyn A. Sharples
    • 2
  • Marc-Antoine Sani
    • 1
  • Roy Michael Robins-Browne
    • 3
    • 4
  • John D. Wade
    • 1
    • 5
  • Frances Separovic
    • 1
  • Mohammed Akhter Hossain
    • 1
    • 5
  1. 1.School of Chemistry, Bio21 InstituteUniversity of MelbourneMelbourneAustralia
  2. 2.Department of Biochemistry and Molecular Biology, Bio21 InstituteUniversity of MelbourneMelbourneAustralia
  3. 3.Department of Microbiology and Immunology, Peter Doherty InstituteUniversity of MelbourneMelbourneAustralia
  4. 4.Murdoch Childrens Research Institute, Royal Children’s HospitalParkvilleAustralia
  5. 5.The Florey Institute of Neuroscience and Mental HealthUniversity of MelbourneMelbourneAustralia

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