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Peptides. 2001 Oct;22(10):1675-81.

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

Author information

1
Department of Organic Chemistry, The Weizmann Institute of Science, Rehovot 76100, Israel.

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.

PMID:
11587796
DOI:
10.1016/s0196-9781(01)00503-4
[Indexed for MEDLINE]

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