Enhanced capture of bacteria and endotoxin by antimicrobial WLBU2 peptide tethered on polyethylene oxide spacers.

Severe sepsis is a life threatening immune response that may be caused by endotoxins (lipopolysaccharides) in circulating bacterial cell wall fragments. Hemoperfusion through a sorbent column coated with the antimicrobial peptide polymyxin B (PMB) is a promising treatment for sepsis. However, PMB is cytotoxic and neurotoxic, and is a membrane disruptor that may fragment endotoxin vesicles. In addition, the blood is not protected from nonspecific interactions with the synthetic surface of the solid support. These effects may be responsible for the variety of undesirable clinical outcomes, including nonspecific adsorption of proteins, blood cell damage, platelet activation, and a lack of clear evidence of efficacy of the current hemoperfusion products. An alternative endotoxin-binding agent is WLBU2, a synthetic cationic amphiphilic peptide that exhibits better selectivity for bacterial cell membranes and reduced host cell cytotoxicity. Tethering the peptide at the periphery of a hydrophilic polyethylene oxide (PEO) brush should also mask the underlying surface, preventing cell and protein adsorption, and is expected to increase the solvent accessibility and molecular mobility of the tethered peptides. WLBU2 tethered on pendant PEO chains exhibited significantly greater capture of intact bacterial cells and endotoxin than surface-immobilized WLBU2. Tethered WLBU2 also captured amounts of endotoxin comparable to PMB. These results suggest that PEO-tethered WLBU2 coatings may be safer and more effective than the state-of-the-art PMB-based technology.