In lipopolysaccharide synthesis

The occurrence of this group of sugar nucleotides is limited mainly to the cells of Gram-negative bacteria. Those bacterial mutants defective in lipopolysaccharide synthesis are useful for preparative isolation of such esters, as the concentration of sugar nucleotides in normal cells is very low. 

Regioselective oxidation by brominolysis of dioxastannolane obtained from methyl / -L-ara-binopyranoside made it possible to accomplish (after subsequent oximation and reduction) a facile synthesis of 4-amino-4-deoxy-L-arabinose, an amino-sugar found in lipopolysaccharides of some Salmonella R. mutant strains <83CPB3778>. 

Lipopolysaccharide had no effect on the protein synthesis ([ HJleucine incorporation) of HC cultured alone. A number of studies concluded that this decrease in protein synthesis was not due to a single cytokine, eicosanoid, or oxygen radical (West et al., 1989). Also, the activity could not be transferred in conditioned supernatant for KC stimulated with LPS alone. However, when... 

In Figure 1, the structures of the Ra to Re lipopolysaccharides have been indicated. These incomplete lipopolysaccharides which are devoid of O chains and parts of the core are formed by R mutant strains which are defective in the synthesis of the O chain (Ra) or of the core (Rb-Re) (reviewed by Luderitz et al., 1982). Ra to Re lipopolysaccharides represent intermediates in lipopolysaccharide biosynthesis. They express distinct serological specificities since the respective terminal sugar units act as the main immunodeterminant. The different R lipopolysaccharides and the respective R mutants, therefore, can be differentiated by serological methods. 

In vivo measurements of lipopolysaccharide synthesis in E. coli B have indicated that two nanomoles of KDO must be synthesized per minute per mg of protein in order to meet the cellular requirement for LPS synthesis under the normal conditions of growth on glucose-minimal medium (27). We have measured the specific activities of the enzymes involved in KDO synthesis in crude extracts of E. coli B including those enzymes responsible for the synthesis of D-ribulose-5-phosphate, the precursor of D-arabinose-5-phosphate. D-Ribulose-5-phosphate is a key intermediate in carbohydrate metabolism as shown in Figure 2, since it is the direct precursor of both D-ribose-5-phosphate and D-arabinose-5-phosphate... 

The presence in bacterial lipopolysaccharides of phosphoryl-ated ethanolamine residues (1) prompted us to experiment with the incorporation of this group. When compound was treated with an activated phosphorylethanolamine derivative, prepared by the procedure shown in Figure 8, the a-phosphate [a]j) +66.7° (chloroform), was obtained in 46% yield. The reaction is similar to that with dibenzyl tributylstannyl phosphate. Thus, the new phosphorylation method may have wide application in the synthesis of C-l phosphorylated lipid A analogs. 

Jack bean a-mannosidase has also been able to catalyze the transglycosylation of rhamnose residue. It has been used in the synthesis of a disaccharide Rhaal,2RhaaSEt in 32.1% yield from RhaapNP and ethyl 1-thio-a-D-rhamnopyranoside. The disaccharide product is a derivative of the common oligosaccharide unit of antigenic lipopolysaccharides from Pseudomonas (33). 

Causes The following causes are seen as being responsible for an acquired immune deficiency syndrome in liver cirrhosis (B.A. Runyon, 1995) (i.) hypofunction of the RES (a decrease in the filter or clearance function and phagocytosis capacity as well as reduced formation of immune modulators) (s. p. 65), (2.) reduction in hepatic synthesis of opsonins (s. p. 66), (3.) compromised function of leucocytes, (4.) impaired proliferation and activation of T lymphocytes, and (5.) increased mucosa permeability to bacteria. Both bacteria and bacterial lipopolysaccharides enter the organism in large numbers. They are responsible for increased serum levels of the cytokines (e. g. interleukins 1 and 6, TNF, y-interferon), and there is increased production of these substances together with their reduced breakdown in the cirrhotic liver. Cytokines are formed in the monocytes of blood and in the mononuclear cells of various organs (above all in ascites). 

Another interesting antibiotic constmct is a peptide-conjugated form of j8-KDO. jS-KDO is an inhibitor of the CMP-KDO synthetase that is involved in lipopolysaccharide (LPS) synthesis, a major constituent of the bacterial cell wall. Antibacterial activity is thus accomplished by interference with cell wall construction. /3-KDO is incapable of membrane permeation, and therefore is not useful as an antibiotic in its native form. Hammond et al. have shown that conjugation of a /3-KDO analog to certain dipeptides resolves this problem [184] (O Fig. 14). Attachment of the /3-KDO analog to a dipeptide allows the glycopeptide constmct to permeate the bacterial membrane. Inside the cell, proteases hydrolyze the peptide and release the inhibitor, resulting ultimately in bacterial cell death. 

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. 

KDO synthetase catalyzes the reaction of arabinose 5-phosphate (29 Ara-5-P) and phosphoenol pyruvate (PEP) to form KDO-8-P (30 Scheme 9). KDO synthetase is not commercially available but has been isolated from E. coli and used in the synthesis of KDO-8-P (63% from Ara-5-P, 38 mmol). KDO-8-P is a key intermediate in the synthesis of the lipopolysaccharide region of Gram-negative bacteria (LPS). Inhibitors of LPS biosynthesis are targets for the design of antimicrobial drugs. ... 

Gram-positive bacteria contain a rigid peptidoglycan cell wall surrounding the cytoplasmic membrane. Gram-negative bacteria contain an additional third, outer layer. This wall is a complex structure with lipoproteins and lipopolysaccharides. Synthesis of two outer walls from different bacterial cells is described in this concept screen ... 

Peptidoglycan Assembly Lipopolysaccharide Synthesis (in Salmonella and Related Genera)... 

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