Chemical synthesis and immunological activities of glycolipids structurally related to lipid A

Abstract

Complete chemical syntheses of a number of monosaccharides derived from 2-deoxy-2-[(3R)-3-hydroxytetradecanamido]-D-glucopyranose and structurally related to the hydrophobic moiety (lipid A) of several bacterial endotoxins are described. Selected humoral (complement activation) and cellular (mitogenicity and induction of interleukin 1 production) in vitro activities of a lipid A preparation obtained from the Bordetella pertussis endotoxin were compared with those of ten of these monosaccharides and with those of previously synthesized, analogous disaccharides. Results show that each of these in vitro activities of the lipid A preparation can be efficiently induced by at least one of the monosaccharide derivatives.

Structural Basis for Interactions between Lung Surfactant Protein C and Bacterial Lipopolysaccharide

“…Synthetic Lipid A Analogs and Peptides-The syntheses of the monosaccharide-derived lipid A analogs, performed by D. Charon and M. Mondange, have been described previously (26). Synthetic analogs of human and mouse SP-C were prepared as described earlier (27)(28)(29)(30)(31).…”

“…The loading of SP-C-(1-21) by the lipid vesicles, however, remains very high, and the results in Table II show that 400 pmol of this peptide (356 pmol actually on the vesicles) does not bind LPS. Therefore, unlike the palmitoyl residues, the last 13 amino acids of the polypeptide chain of SP-C (amino acids [22][23][24][25][26][27][28][29][30][31][32][33][34][35], representing the Cterminal hydrophobic region of the molecule, play a critical role in LPS binding. In contrast, vesicles containing even lower amounts (200 pmol) of peptides SP-C(Leu) and SP-C(LKS), which contain the hydrophobic region, bind LPS as efficiently as those with natural porcine SP-C. Because SP-C-(1-21) was the only synthetic peptide that did not bind LPS when used at the same concentration as that the four others, we analyzed vesicles in which higher amounts of this peptide were incorporated.…”

Preexposure of mouse peritoneal macrophages to lipopolysaccharide and other stimuli enhances the nitric oxide response to secondary stimuli

“…The glucosamine-derived glycolipids M4 [16] and DM4 ( Fig. 1), synthesized by D. Charon and M. Mondange, were used as described previously [3].…”

Molecular adjuvants and immunomodulators: new approaches to immunization

“…A monosaccharide derivative of the basic structure of lipid A also has been shown by Charon et al to induce IL-1 (16). Dijkstra et al (31) reported that the incorporation of lipid A (from an Rc mutant) or monophosphoryl lipid A into liposomes reduced by 12,000-fold their IL-1-inducing capacity, suggesting that a direct interaction of the lipid A with the macrophage membrane was required for this property.…”