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Updated: Aug 30, 2026

Production and Visualization of Bacterial Spheroplasts and Protoplasts to Characterize Antimicrobial Peptide Localization
10:13

Production and Visualization of Bacterial Spheroplasts and Protoplasts to Characterize Antimicrobial Peptide Localization

Published on: August 11, 2018

Modulation of the hydrophobic domain of polymyxin B nonapeptide: effect on outer-membrane permeabilization and

Haim Tsubery1, Itzhak Ofek, Sofia Cohen

  • 1Department of Organic Chemistry, the Weizmann Institute of Science, Rehovot, Israel.

Molecular Pharmacology
|October 23, 2002
PubMed

Insights

The hydrophobic segment of Polymyxin B nonapeptide (PMBN) is crucial for its ability to increase bacterial outer membrane permeability. Modifications to this segment significantly impact LPS binding and antibacterial activity.

Area of Science:

  • Microbiology
  • Peptide Chemistry
  • Drug Discovery

Background:

  • Polymyxin B nonapeptide (PMBN) enhances Gram-negative bacteria outer membrane permeability to hydrophobic antibiotics.
  • The hydrophobic segment (D-Phe(5)-Leu(6)) of PMBN is hypothesized to be key to its activity.

Purpose of the Study:

  • To investigate the role of the PMBN hydrophobic segment in lipopolysaccharide (LPS) binding and outer membrane permeability.
  • To synthesize and evaluate PMBN analogs with modifications to the hydrophobic residues D-Phe(5) and Leu(6).

Main Methods:

  • Synthesis of four PMBN analogs: [D-Trp(5)]PMBN, [D-Tyr(5)]PMBN, [Phe(6)]PMBN, and [Ala(6)]PMBN.
  • Evaluation of LPS binding affinity using IC(50) values.
  • Assessment of bacterial outer membrane permeability and LPS neutralization activity.

Main Results:

  • [D-Tyr(5)]PMBN and [Ala(6)]PMBN showed reduced LPS affinity and significantly decreased outer membrane permeability.
  • [Phe(6)]PMBN exhibited LPS affinity and outer membrane permeability comparable to PMBN.
  • [D-Trp(5)]PMBN had similar LPS affinity but moderately reduced outer membrane permeability compared to PMBN.

Conclusions:

  • The hydrophobic segment of PMBN plays a significant role in its biological activity.
  • Specific modifications to D-Phe(5) and Leu(6) residues can modulate PMBN's interaction with LPS and its ability to permeabilize the bacterial outer membrane.

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