Comparison of endotoxin antagonism of linear and cyclized peptides derived from limulus anti-lipopolysaccharide factor.

Background: Limulus anti-lipopolysaccharide (LPS) factor (LALF) is a 102-amino acid LPS-binding protein from the horseshoe crab, Limulus polyphemus. The peptide includes the LPS-binding domain of holoLALF, yet it lacks the loop structure stabilized by disulfide or other covalent bonds that is a common motif in the LPS-binding regions of holo- LALF and several other LPS-binding proteins. Although it neutralizes LPS and is bactericidal against Pseudomonas aeruginosa, the LALF 28-54 portion of LALF is not protective in a murine model of intraperitoneal sepsis compared with holoLALF.

Molecular biology of endotoxin antagonism.

The development of new therapies for the treatment of gram-negative bacterial sepsis has been the focus of extensive investigation. Molecular and cellular biologic techniques have led to important advances, including (1) identification of naturally occurring lipopolysaccharide (LPS)-binding proteins; (2) generation of novel LPS-binding antibodies, proteins, and peptides; and (3) characterization of the molecular determinants of LPS binding. In composite, these advances have facilitated comprehension of the manner in which gram-negative bacterial infection and concurrent endotoxemia exert detrimental effects on the mammalian host.