Sushi Peptide S3 is a trimer of one of the high endotoxin-binding domains, Sushi 3 (or S3) within Factor C, a lipopolysaccharide (LPS)-sensitive serine protease of the horseshoe crab (Limulus Polyphemus). S3 display detergent-like properties in disrupting LPS aggregates, with specificity for palmitoyl-oleoyl-phosphatidylglycerol (POPG) resulting from electrostatic and hydrophobic forces between the peptides and the bacterial lipids. The unsaturated nature of POPG confers fluidity and enhances insertion of the peptides into the lipid bilayer, causing maximal disruption of the bacterial membrane. In short, peptide S3 can bind to lipopolysaccharide (LPS) and inhibit the growth of Gram-negative bacteria without affecting mammalian cells. It has been shown that endotoxin activates Factor C based catalytic coagulation cascade resulting in the gelation of Limulus blood. This process is the basis of Limulus Amebocyte Lysate (LAL) endotoxin detection method.
