European Biophysics Journal

, Volume 40, Issue 4, pp 555–564

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

Authors

  • Mohammed Akhter Hossain
    • Florey Neuroscience Institutes and School of ChemistryUniversity of Melbourne
  • Laure Guilhaudis
    • Laboratoire de Chimie Organique Biologique et Structurale, CNRS UMR 6014, COBRA, European Institute for Peptide ResearchUniversité de Rouen
  • Agnes Sonnevend
    • Department of Medical Microbiology, Faculty of Medicine and Health SciencesUnited Arab Emirates University
  • Samir Attoub
    • Department of Pharmacology, Faculty of Medicine and Health SciencesUnited Arab Emirates University
  • Bianca J. van Lierop
    • School of ChemistryMonash University
  • Andrea J. Robinson
    • School of ChemistryMonash University
  • John D. Wade
    • Florey Neuroscience Institutes and School of ChemistryUniversity of Melbourne
    • Department of Biochemistry, Faculty of Medicine and Health SciencesUnited Arab Emirates University
Original Paper

DOI: 10.1007/s00249-011-0679-2

Cite this article as:
Hossain, M.A., Guilhaudis, L., Sonnevend, A. et al. Eur Biophys J (2011) 40: 555. doi:10.1007/s00249-011-0679-2

Abstract

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 Candidaalbicans 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).

Keywords

Antibacterial and antifungal peptideBrevinin-1Dicarba bondCytotoxicityRing-closing metathesis

Abbreviations

CFU

Colony forming units

DC

Dicarba

DMF

Dimethylformamide

MDRAB

Multidrug-resistant Acinetobacter baumannii

MRSA

Methicillin-resistant Staphylococcus aureus

RCM

Ring-closing metathesis

TFA

Trifluoroacetic acid

TFE

Trifluoroethanol

Copyright information

© European Biophysical Societies' Association 2011