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Lipid A, the lipid component of bacterial lipopolysaccharides: Relation of chemical structure to biological activity

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Summary

Lipopolysaccharides are integral components of the outer membrane of Gram-negative bacteria and they participate in various membrane functions essential for bacterial growth and survival. Lipopolysaccharides also represent the endotoxins of Gram-negative bacteria and possibly play a role for the pathogenesis and manifestations of bacterial infections. These biological activities are mediated mainly by the lipid component of lipopolysaccharides, termed lipid A. Chemically, lipid A consists of a β1,6-linkedD-glucosamine disaccharide which carries substituted phosphoryl groups and a range ofD-3-hydroxy andD-3-acyloxyacyl residues, the latter being arranged in a hexagonal dense packing.

A number of experimental data allow the conclusion that the highly ordered and compact lipid A structure confers stability to the outer membrane, renders it less permeable to lipophilic molecules and by providing a proper fluidity stabilizes the conformation of biologically active membrane proteins. For endotoxic activities of lipid A the polar substituents of phosphate residues are dispensable. The presence ofD-3-hydroxy (or acyloxy) acyl-groups, linked to the glucosamine disaccharide, however, seems to be of importance. Analyses of now available synthetic lipid A analogues are expected to allow a more precise characterization of substructures and conformations required for the expression of physiological functions and endotoxic activities of lipid A.

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Rietschel, E.T., Wollenweber, HW., Zähringer, U. et al. Lipid A, the lipid component of bacterial lipopolysaccharides: Relation of chemical structure to biological activity. Klin Wochenschr 60, 705–709 (1982). https://doi.org/10.1007/BF01716559

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