Lipopolysaccharide of Gram-negative

Fever is the most common manifestation. The thermoregulatory centre in the hypothalamus regulates body temperature and this can be affected by endotoxins (heat-stable lipopolysaccharides) of Gram-negative bacteria and also by a monokine secreted by monocytes and macrophages called interleukin-1 (IL-1) which is also termed endogenous pyrogen. Antibody production and T-cell proliferation have been shown to be enhanced at elevated body temperatures and thus are beneficial effects of fever. 

Some examples of transformations involving carbonyl ylides are listed in Table 4.20. Entry 1 illustrates the conversion of P-acyloxy-a-diazoesters into a-acyloxyacrylates by ring fission of a cyclic carbonyl ylide [978]. This reaction has been used for the synthesis of the natural aldonic acid KDO (3-deoxy-Z)-manno-2-octulosonic acid), which is an essential component of the cell wall lipopolysaccharide of gram-negative bacteria (Figure 4.15). 

Cell-wall lipopolysaccharides of Gram-negative bacteria (Shigella strains) have also been purified by gel chromatography.122 These... 

Immunostimulatory adjuvants exert their effects predominantly at the cytokine level or through the activation of costimulatory signals. The type of response required for optimal protection depends on the pathogen. One class of immunostimulatory adjuvants is derived from the lipopolysaccharide of gram-negative bacteria. The most extensively evaluated member of this family, monophosphoryl lipid A (MPL), is obtained from Salmonella minnesota. MPL has been shown to induce the synthesis and release of cytokines, which promote the generation of specific immune responses. 

The six-carbon chain of ManNAc 6-P can be extended by three carbon atoms using an aldol-type condensation with a three-carbon fragment from PEP (Eq. 20-7, step c) to give N-acetylneuraminic acid (sialic acid).48 Tire nine-carbon chain of this molecule can cyclize to form a pair of anomers with 6-membered rings as shown in Eq. 20-7. In a similar manner, arabi-nose 5-P is converted to the 8-carbon 3-deoxy-D-manno-octulosonic acid (KDO) (Fig. 4-15), a component of the lipopolysaccharide of gram-negative bacteria (Fig. 8-30), and D-Erythrose 4-P is converted to 3-deoxy-D-arafrmo-heptulosonate 7-P, the first metabolite in the shikimate pathway of aromatic synthesis (Fig. 25-1).48a The arabinose-P used for KDO synthesis is formed by isomerization of D-ribulose 5-P from the pentose phosphate pathway, and erythrose 4-P arises from the same pathway. 

Polymers having carbohydrate chains linked to a lipid anchor embedded in a bacterial membrane the term bacterial amphiphiles was suggested5 for these polymers. Lipopolysaccharides of Gram-negative bacteria constitute the best-known example of these polymers. 

Luderitz, O., Freudenberg, M.A., Galanos, C., Lehmann, V., Rietschel, E.Th, and Shaw, D.H. (1982). Lipopolysaccharides of Gram-negative bacteria. In Microbial Membrane Lipids (Razin, S., and Rottem, S., eds.). Current Topics in Membranes and Transport., J 7, 79-151. Academic Press Inc., New York... 

Y. A. Knirel and N. K. Kochetkov, The structure of the lipopolysaccharides of Gram-negative bacteria. I. General characterization of the lipopolysaccharides and the structure of lipid A, Biochemistry (Moscow), 58 (1993) 73-84. 

Knirel, Y.A., Kochetkov, N.K. The structure of lipopolysaccharides of Gram-negative bacteria. III. The strcucture of O antigens a review. Biochemistry (Moscow) 59 (1994) 1325-1383. 

Glycero-u-manno-heplose is a monosaccharide residue found in bacterial polysaccharides, predominantly in the inner core region of lipopolysaccharides of Gram-negative bacteria. The h-glycero form is the most abundant, but the D-glycero isomer has also been found [1,2]. 

The key component of the cell wall lipopolysaccharide of Gram-negative bacteria, KDO (3-deoxy-D-manno-2-octulosonic acid), was synthesized by S.D. Burke and co-workers. One of the key transformations in the synthetic sequence was a doubie SAD of a 6-vinyldihydropyran-2-carboxylate template. This 1,4-diene was cleanly converted to a mixture of two C7 epimeric tetraols in a 20 1 ratio. The endocyclic olefin had an intrinsic preference for dihydroxyiation from the 3-face and not from the desired a-face. This stereofacial bias was impossible to override with any ligand normally used in the SAD, so later in the synthesis these two stereocenters had to be inverted in order to give the required stereochemistry at C4 and C5. 

Although amino acid 1 is a potent inhibitor of CMP-KDO synthase (Figure 36.21), a key enzyme in the biosynthesis of the lipopolysaccharide of Gram-negative bacteria, it is unable to reach its cytoplasmic target and is therefore inactive as an antibacterial agent. Simple lipophilic esters are not useful to enhance the delivery of amino acid 1 since they are not cleaved by the bacteria. On the other hand, double prodrug 3 has been found to solve the problem. ... 

Cell-wall Lipopolysaccharides of Gram-negative Bacteria. 409... 

Naberezhnykh, G. A., Gorbach, V. L, Likhatskaya, G. N., Davidova, V. N., and Solov eva, T. F. 2008. Interaction of chitosan and their A-acylated derivatives with lipopolysaccharide of gram-negative bacteria. Biochemistry 73 432-441. 

C,8H3oOi6 502.425 Constit. of lipopolysaccharide of gram negative bacteria, e.g. capsular polysaccharide of E. coli strain LP 1092. 

Component of the lipopolysaccharides of gram-negative bacteria Rhodopseudomo-... 

An inversion of diastereoselectivity occurred when using acetonide-protected aldoses (Binder et al, 1994). This observation was exploited for a rapid synthesis (Scheme 4.5) of 3-deoxy-D-manno-2-octulosonic acid (KDO), the key constituent of the lipopolysaccharides of Gram-negative bacteria (Gao et al, 1994). 

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