(618av) Parallel Synthesis and Screening of Polymers with Endotoxin Binding Activities

A component of the outer membrane of Gram-negative bacteria, lipopolysaccharides are toxic to the health of humans and animals. Lipopolysaccharides are endotoxins and cause strong immunological responses in normal individuals. Responses include inflammation and fever, leading to septic shock, which can result in death. Sequestration of lipopolysaccharides (endotoxin) is therefore of critical importance in therapeutic interventions and decontamination applications. A library of polymers was screened in order to rapidly identify lead candidates that bind endotoxin. A fluorescence-based parallel screening assay was employed to screen the polymer library. In this assay, the displacement of a fluorescent dye that binds specifically to the toxic lipid area of a lipopolysaccharide was used as an indicator of polymer-endotoxin binding. In addition to polymer type and dose, the role of different physicochemical factors including salt concentration and pH on polymer-endotoxin binding was investigated. Several polymers that demonstrated high efficacies for endotoxin binding were identified. Lead polymers were further characterized using FT-IR and NMR spectroscopy, and their ability to bind endotoxin was demonstrated additional experimental methods. Our results indicate that parallel synthesis and screening approaches can lead to the rapid identification of polymers for endotoxin sequestration.