title: 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 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 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.
authors.affiliation: Forschungszentrum Borstel, Leibniz-Zentrum für Medizin und Biowissenschaften, D-23845 Borstel, Germany.
authors.forename: Ina
authors.initials: I
authors.lastname: Kowalski
authors.forename: Yani
authors.initials: Y
authors.lastname: Kaconis
authors.forename: Jörg
authors.initials: J
authors.lastname: Andrä
authors.forename: Iosu
authors.initials: I
authors.lastname: Razquin-Olazarán
authors.forename: Thomas
authors.initials: T
authors.lastname: Gutsmann
authors.forename: Guillermo
authors.initials: G
authors.lastname: Martinez de Tejada
authors.forename: Klaus
authors.initials: K
authors.lastname: Brandenburg
mesh_terms: D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000494:pharmacology; D060829:Arthropod Proteins; D002151:Calorimetry; D002478:Cells, Cultured; D006801:Humans; D007447:Invertebrate Hormones / Q000737:chemistry* / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008055:Lipids / Q000737:chemistry*; D008070:Lipopolysaccharides / Q000737:chemistry / Q000494:pharmacology; D008969:Molecular Sequence Data; D044367:Phase Transition; D017433:Protein Structure, Secondary; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D023181:Antimicrobial Cationic Peptides; D060829:Arthropod Proteins; D007447:Invertebrate Hormones; D008055:Lipids; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C034705:antilipopolysaccharide factor (Limulus)