ABSTRACT
This chapter focuses on pharmaceutically acceptable antagonist that would interact with the putative lipopolysaccharide (LPS) receptor on the cell surface and block the action of LPS without demonstrating any “LPS-like” cellular activation on its own. Synthetic endotoxin antagonists are structurally based on natural lipid A and the biosynthetic precursors. The decrease in activity from this last alteration is proposed to be due to the steric bulk of this modification, thus causing a drastic conformational change in the molecule, and due to the electronics at the C-4 position. Since the structure of lipid IVA presents a synthetically simpler disaccha-ride, the investigation into the feasibility of using this biosynthetic intermediate began as a lead structure. Bacterial infection can be life-threatening, requiring that a potential host organism be highly diligent in maintaining its antimicrobial “state of awareness.” Endotoxin or LPS is an integral component of the outer membrane of gram-negative bacteria.
