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

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

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 [Agl 18,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 [Ser 18,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).

Original languageEnglish
Pages (from-to)555-564
Number of pages10
JournalEuropean Biophysics Journal
Volume40
Issue number4
DOIs
Publication statusPublished - Apr 2011

Keywords

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

ASJC Scopus subject areas

  • Biophysics

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