Biophysical mechanisms of the neutralization of endotoxins by lipopolyamines

Diptesh Sil, Lena Heinbockel, Yani Kaconis, Manfred Rössle, Patrick Garidel, Thomas Gutsmann, Sunil A. David, Klaus Brandenburg

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Endotoxins (lipopolysaccharides, LPS) are one of the strongest immunostimulators in nature, responsible for beneficial effects at low, and pathophysiological effects at high concentrations, the latter frequently leading to sepsis and septic shock associated with high mortality in critical care settings. There are no drugs specifically targeting the patho-physiology of sepsis, and new therapeutic agents are therefore urgently needed. The lipopolyamines are a novel class of small molecules designed to sequester and neutralize LPS. To understand the mechanisms underlying the binding and neutralization of LPS toxicity, we have performed detailed biophysical analyses of the interactions of LPS with candidate lipopolyamines which differ in their potencies of LPS neutralization. We examined gel-to-liquid crystalline phase behavior of LPS and of its supramolecular aggregate structures in the absence and presence of lipopolyamines, the ability of such compounds to incorporate into different membrane systems, and the thermodynamics of the LPS:lipopolyamine binding. We have found that the mechanisms which govern the inactivation process of LPS obey similar rules as found for other active endotoxin neutralizers such as certain antimicrobial peptides.

Original languageEnglish (US)
Pages (from-to)82-93
Number of pages12
JournalOpen Biochemistry Journal
Volume7
Issue number1
DOIs
StatePublished - 2013

Keywords

  • Endotoxins
  • Inflammation
  • Lipopolyamines
  • Lipopolysaccharide
  • Sepsis

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