SALP (Pep19-4) peptide

Synthetic Antilipopolysaccharide Peptides (SALPs) are with various gram-negative and gram-positive bacteria, including resistant strains. The analysis of antimicrobial activity by conventionaltechniques and atomic force microscopy showed a strict dependenceon amino acid (aa) sequences, with the type of amino acid, its positionwithin the primary structure, and the sequence length being critical parameters.By monitoring lipopolysaccharide (LPS)- or bacteria-induced cytokineproduction in human mononuclear cells and whole blood, we found adirect link between the binding of the lead compound Pep19-2.5 to Salmonellaenterica and the anti-inflammatory activity of the peptide. Thermodynamicanalysis of Pep19-2.5 binding to the bacterial cell envelopeshowed an exothermic reaction with saturation characteristics, whereassmall-angle X-ray scattering data indicated a direct attachment of Pep19-2.5 to the bacterial cell envelope. This binding preferentially takes place tothe LPS outer monolayer, as evidenced by the change in the LPS acylchain and phosphate vibrational bands seen by Fourier-transform infraredspectroscopy. We report here that the anti-inflammatory activity of Pep19-2.5 is not only connected with neutralization of cell-free bacterial toxinsbut also with a direct binding of the peptide to the outer leaflet of the bacterialouter membrane.