European Biophysics Journal

, Volume 40, Issue 4, pp 555–564 | Cite as

Synthesis, conformational analysis and biological properties of a dicarba derivative of the antimicrobial peptide, brevinin-1BYa

  • Mohammed Akhter Hossain
  • Laure Guilhaudis
  • Agnes Sonnevend
  • Samir Attoub
  • Bianca J. van Lierop
  • Andrea J. Robinson
  • John D. Wade
  • J. Michael Conlon
Original Paper


Brevinin-1BYa (FLPILASLAAKFGPKLFCLVTKKC), first isolated from skin secretions of the frog Rana boylii, displays broad-spectrum antimicrobial activity and potent haemolytic activity. This study investigates the effects on conformation and biological activity of replacement of the intramolecular disulphide bridge in the peptide by a non-reducible dicarba bond. Dicarba-brevinin-1BYa was prepared by microwave irradiation of [Agl18,Agl24]-brevinin-1BYa (Agl = allylglycine) in the presence of a second generation Grubbs’ catalyst. Circular dichroism spectroscopy in 50% trifluoroethanol-water indicated that the degree of α-helicity of the dicarba derivative (22%) was less than that of brevinin-1BYa (27%) but comparable to that of the acyclic derivative [Ser18,Ser24]-brevinin-1BYa (23%). Dicarba-brevinin-1BYa showed a two-fold increase in potency against reference strains of Escherichia coli, Staphylococcus aureus, and Candida albicans compared with the native peptide and displayed potent bactericidal activity against clinical isolates of methicillin-resistant S. aureus (MRSA) and multidrug-resistant Acinetobacter baumannii (MIC in the range 1–8 μM). Compared with brevinin-1BYa and [Ser18,Ser24]-brevinin-1BYa, the dicarba derivative was associated with increased cytotoxicity against human erythrocytes (2.5-fold), MDA-MB-231 breast carcinoma cells (1.3-fold) and HepG2 hepatoma-derived cells (1.5-fold).


Antibacterial and antifungal peptide Brevinin-1 Dicarba bond Cytotoxicity Ring-closing metathesis 



Colony forming units






Multidrug-resistant Acinetobacter baumannii


Methicillin-resistant Staphylococcus aureus


Ring-closing metathesis


Trifluoroacetic acid





The authors thank Eman Ahmed, Milena Mechkarska, Kholoud Arafat and Annie Sunny (United Arab Emirates University) for technical assistance in this study. This work was supported by a Faculty Support Grant from the United Arab Emirates University.


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Copyright information

© European Biophysical Societies' Association 2011

Authors and Affiliations

  • Mohammed Akhter Hossain
    • 1
  • Laure Guilhaudis
    • 2
  • Agnes Sonnevend
    • 3
  • Samir Attoub
    • 4
  • Bianca J. van Lierop
    • 5
  • Andrea J. Robinson
    • 5
  • John D. Wade
    • 1
  • J. Michael Conlon
    • 6
  1. 1.Florey Neuroscience Institutes and School of ChemistryUniversity of MelbourneMelbourneAustralia
  2. 2.Laboratoire de Chimie Organique Biologique et Structurale, CNRS UMR 6014, COBRA, European Institute for Peptide ResearchUniversité de RouenMont-Saint-AignanFrance
  3. 3.Department of Medical Microbiology, Faculty of Medicine and Health SciencesUnited Arab Emirates UniversityAl-AinUAE
  4. 4.Department of Pharmacology, Faculty of Medicine and Health SciencesUnited Arab Emirates UniversityAl-AinUAE
  5. 5.School of ChemistryMonash UniversityClaytonAustralia
  6. 6.Department of Biochemistry, Faculty of Medicine and Health SciencesUnited Arab Emirates UniversityAl-AinUAE

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