Biophysical Mechanisms of the Neutralization of Endotoxins by Lipopolyamines
| Autor: | Diptesh Sil, Klaus Brandenburg, Manfred Rössle, Patrick Garidel, Yani Kaconis, Lena Heinbockel, Sunil A. David, Thomas Gutsmann |
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| Rok vydání: | 2013 |
| Předmět: |
Lipopolysaccharide
Antimicrobial peptides Inflammation Article General Biochemistry Genetics and Molecular Biology Neutralization Sepsis 03 medical and health sciences chemistry.chemical_compound medicine 030304 developmental biology 0303 health sciences 030306 microbiology Septic shock medicine.disease Small molecule Lipopolyamines 3. Good health Endotoxins chemistry Biochemistry Immunology Toxicity lipids (amino acids peptides and proteins) medicine.symptom |
| Zdroj: | The Open Biochemistry Journal |
| ISSN: | 1874-091X |
| DOI: | 10.2174/1874091x01307010082 |
| Popis: | 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 behav- ior 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. |
| Databáze: | OpenAIRE |
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