Physicochemical and Biological Characterization of Anti-Endotoxin Peptides and Their Influence on Lipid Properties
Abstract:We have synthesized a series of short peptides (17 to 20 amino acids), originally derived from Limulus antilipopolysaccharide factor LALF, which were primarily designed to act as antimicrobial agents as well as neutralizers of bacterial endotoxin (lipopolysaccharide, LPS), Here, two selected peptides, a 17- and a 19-mer, were characterized physicochemically and in biological test systems. The secondary structure of the peptides indicates essentially a β-sheet including antiparallel strands, the latter being reduced when the peptides bind to LPS. A very strong exothermic binding due to attractive Coulomb interactions governs the LPS-peptide reaction, which additionally leads to a fluidization of the acyl chains of LPS. A comparison of the interaction of the peptide with negatively charged phosphatidylserine shows in contrast a rigidification of the acyl chains of the lipid. Finally, the biological assays reveal a diverging behaviour of the two peptides, with higher antibacterial activity of the 17-mer, but a much higher activity of the 19-mer in its ability to inhibit the LPS-induced cytokine production in human mononuclear cells.
Keywords: (AMPs); (DMPS); (ITC); (MIC); (MNC); (PS); (TNF); AEP; ELISA; FTIR Spectroscopy; Gram-negative bacteria; HEPES buffer; LALF; LPS; Lipid; MIC; RP-HPLC; Sepsis; antimicrobial peptides; isothermal; isothermal titration calorimetry
Document Type: Research Article
Publication date: 2010-11-01
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