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Updated: Jul 28, 2025

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Interaction of Pexiganan (MSI-78)-Derived Analogues Reduces Inflammation and TLR4-Mediated Cytokine Secretion: A

Hadar Cohen1, Naiem Ahmad Wani1, Daniel Ben Hur1

  • 1Department of Biomolecular Sciences, The Weizmann Institute of Science, Rehovot 76100, Israel.

ACS Omega
|May 30, 2023
PubMed

Insights

New antimicrobial peptides (AMPs) were designed to combat antibiotic-resistant bacteria and sepsis. These peptides neutralize endotoxins, reduce toxicity, and show potential for treating sepsis and bacterial infections.

Area of Science:

  • Microbiology
  • Biochemistry
  • Pharmacology

Background:

  • Antibiotic resistance and sepsis pose significant global health threats.
  • Antimicrobial peptides (AMPs) offer potential for novel antimicrobial and immunomodulatory therapies.
  • Existing treatments for sepsis and resistant infections are limited.

Purpose of the Study:

  • To design and synthesize novel AMPs based on pexiganan (MSI-78).
  • To investigate the antimicrobial activity and endotoxin-neutralizing capacity of these new AMPs.
  • To evaluate the safety profile, including toxicity and hemolytic activity, of the designed peptides.

Main Methods:

  • Synthesis of novel AMPs with segregated charged and hydrophobic regions to mimic lipopolysaccharide (LPS).
  • Antimicrobial activity assays and LPS-induced cytokine release inhibition profiling.
  • Biochemical and biophysical characterization using ATR-FTIR spectroscopy, MST, and electron microscopy.

Main Results:

  • Two novel AMPs, MSI-Seg-F2F and MSI-N7K, were successfully synthesized.
  • These peptides demonstrated preserved endotoxin neutralization activity.
  • Reduced toxicity and hemolytic activity were observed in the new AMPs compared to controls.

Conclusions:

  • The designed AMPs, MSI-Seg-F2F and MSI-N7K, show promise for combating bacterial infections and detoxifying LPS.
  • These peptides represent potential therapeutic candidates for sepsis treatment.
  • Further development could lead to effective strategies against antibiotic-resistant pathogens.

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