N-terminal modifications of Polymyxin B nonapeptide and their effect on antibacterial activity

Haim Tsubery, Itzhak Ofek, Sofia Cohen, Mati Fridkin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

69 Scopus citations

Abstract

Polymyxin B (PMB) is a potent antibacterial lipopeptide composed of a positively charged cyclic peptide ring and a fatty acid containing tail. Polymyxin B nonapeptide (PMBN), the deacylated amino derivative of polymyxin B, is much less bactericidal but able to permeabilize the outer membrane of Gram-negative bacteria and to neutralize the toxic effects of lipopolysaccharide (LPS). In this study, we synthesized and evaluated the antibacterial and LPS neutralizing activities of four PMBN analogs modified at their N-terminal. Our results suggest that oligoalanyl substitutions of PMBN do not effect most of PMBN activities. However, a hydrophobic aromatic substitution generated a PMB-like molecule with high antibacterial activity and significant reduced toxicity.

Original languageEnglish
Pages (from-to)1675-1681
Number of pages7
JournalPeptides
Volume22
Issue number10
DOIs
StatePublished - 2001

Keywords

  • Antibacterial peptide
  • Lipopolysaccharide
  • Polymyxin B
  • Polymyxin B nonapeptide

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