Synthesis and immunological properties of Rhizobium sin-1 lipid A and an oligosaccharide derived from the cell wall of Bacillus anthracis
MetadataShow full item record
LPS from Rhizobium sin-1 (R. sin-1) can antagonize the production of tumor necrosis factor alpha (TNF-α) by E. coli LPS in human monocytic cells. Although these compounds provide interesting leads for the development of therapeutics for septic shock yet, the propensity of these compounds to undergo β-elimination to give biological inactive enone derivatives hampers detailed structure activity relationship studies. To address this problem, we have chemically synthesized in a convergent manner a R. sin-1 lipid A derivative in which the β-hydroxy ester at C-3 of the proximal sugar unit has been replaced by an ether linked moiety. The antagonizing ability against E. coli lipid A and the stability of the synthetic compound has been tested and compared with narural R. sin-1 lipid A. Bacillus anthracis is a gram-positive, spore-forming bacterium that causes anthrax in humans and other mammals. The secondary cell wall of vegetative cells of Bacillus anthracis contains an unusual polysaccharide, which may represent an important target for vaccine and diagnostics development. The antigenic properties of this oligosaccharide have, however, not been studied. We have synthesized two trisaccharides and tested for their affinity toward the antibodies produced from a live- and irradiated spore vaccine and polysaccharide linked to the carrier protein KLH. Finally, to locate important antigenic components of the hexasaccharide we are synthesizing various oligosaccharide fragments. The oligosaccharides are synthesized with an aminopentyl spacer to facilitate conjugation to carrier proteins, which is required for immunization and ELISA.