Concepts of the Chemical Structure of Lipid A

Lipid A represents the covalently bound lipid component of lipopolysaccharides (LPS), the endotoxins and O antigens of gram-negative bacteria. Lipid A's of endotoxically active LPS consist of a beta(1'----6)-linked D-glucosamine disaccharide that carries phosphoryl groups in positions 1 and 4'. Depending on the origin of lipid A, nonacylated, nitrogen-containing residues may be bound to these phosphoryl groups. As shown in enterobacterial lipid A's, available hydroxyl groups of the D-glucosamine disaccharide are substituted by 3-deoxy-D-mannooctulosonic acid (position 6'), (R)-3-hydroxytetradecanoic acid (position 3), and (R)-3-(tetradecanoyloxy)tetradecanoic acid (position 3'). The hydroxyl group at C-4 appears to be free. The amino groups of the disaccharide carry (R)-3-(acyloxy)acyl [and (R)-3-hydroxyacyl] residues in a specific distribution. On the basis of these data, a proposal for a general structure of lipid A is made. As a specific example of this general architecture, the chemical structure of lipid A of Salmonella minnesota LPS is presented.