Physicochemical and biological characterization of anti-endotoxin peptides and their influence on lipid properties

We have synthesized a series of short peptides (17 to 20 amino acids),originally derived from limulus anti-lipopolysaccharide 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 phys-icochemically 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. © 2010 bentham science publishers ltd.