Capsular polysaccharide

Vaccines can be roughly categorized into killed vaccines and Hve vaccines. A killed vaccine can be (/) an inactivated, whole microorganism such as pertussis, (2) an inactivated toxin, called toxoid, such as diphtheria toxoid, or (J) one or more components of the microorganism commonly referred to as subunit vaccines. The examples are capsular polysaccharide of Streptococcus pneumoniae and the surface antigen protein for Hepatitis B vims vaccine. 

Composition and Methods of Manufacture. The vaccine consists of a mixture of purified capsular polysaccharides from 23 pneumococcal types that are responsible for over 90% of the serious pneumococcal disease in the world (47,48). Each of the polysaccharide types is produced separately and treated to remove impurities. The latter is commonly achieved by alcohol fractionation, centrifugation, treatment with cationic detergents, proteolytic en2ymes, nucleases or activated charcoal, diafiltration, and lyophili2ation (49,50). The vaccine contains 25 micrograms of each of the types of polysaccharide and a preservative such as phenol or thimerosal. 

Fungi (whole yeasts capsular polysaccharides proteins)... 

In 1967, Heidelberger, Stacey et al. reported the purification, some structural features, and the chemical modification of the capsular polysaccharide from Pneumococcus Type I. Difficulties of direct hydrolysis of the polysaccharide were overcome and it was possible to identify some of the fragments in the hy-drolyzate. At least six products resulted from nitrous acid deamination. Two were disaccharides, which were identified, and sequences of linked sugar units were proposed. As modification of the polysaccharide decreased the amounts of antibody precipitated by anti-pneumococcal Type I sera, the importance of the unmodified structural features in contributing to the specificity of the polysaccharide was indicated. 

By 1945, Stacey speculated about the possibility of a structural relationship between Pneumococcus capsular polysaccharides and those produced by other organisms. With Miss Schliichterer, he had examined the capsular polysaccharide of Rhizobium radicicolum. This polysaccharide gave a precipitin reaction in high dilution, not only with Type III Pneumococcus antiserum, but also mixed with antisera from other Pneumococcus types. The chemical evidence indicated that the polysaccharide resembled the specific polysaccharides of Types I and II Pneumococcus. A decade later, the acidic capsular polysaccharide from Azoto-bacter chroococcum, a soil organism, was studied. It, too, produced serological cross-reactions with certain pneumococcal specific antisera. Although the molecular structure of the polysaccharide was not established, adequate evidence was accumulated to show a structural relationship to Type III Pneumococcus-specific polysaccharide. This was sufficiently close to account for the Type III serological cross-relationship. 

L-Fucosamine was found as a constituent of Pneumococcus Type V capsular polysaccharide and as a constituent of the mucopolysaccharides (glycosamino-glycans) of certain enteric bacteria A new synthesis was devised to make the amino sugar more available. 

Sulfonamide Drugs and Pneumococcus Capsular Polysaccharides, M. Stacey and E. Schliichterer, Nature. 143 (1939)724. 

Structure of Pneumococcus Capsular Polysaccharides, S. A. Barker and M. Stacey, Biochem. /., 82... 

Note a, b, and e are in A. a = p= 90 and 7 are in degress. a Chitin I and U were originally termed [S- and a-chitin, respectively. b Non-half-staggered double helix. e Capsular polysaccharide. 

Fig. 39.—fa) Stereo view of two turns of the left-handed. 2-fold helix of E. coli capsular polysaccharide (46) stabilized by hydrogen bonds involving both main and side chains. The vertical line represents the helix axis. 

Table A31 Structure 47 Rhizobium trifolii Capsular Polysaccharide ...

Five pentoses, namely, D-ribose, d- and L-arabinose, and D- and L-xylose, have been found in hydrolyzates of bacterial polysaccharides. D-Riboseisthe most common of these, and is a component of different LPS, capsular polysaccharides, and teichoic acid type of polymers. In all these polymers, it occurs as the /I-furanosyl group or residue. 

The type-specific capsular polysaccharide from Streptococcus pneumoniae type 5 contains 2-acetamido-2,6-dideoxy- -D-x>>/o-hexopyranosyl-4-ulose residues (17). Sugar nucleotides of hexos-4-uloses are important intermediates in the transformation of sugars during the biosynthesis, but this is the only known example of such a sugar as a polysaccharide component. 

The capsular polysaccharide from Rhizobium meliloti IFO 13336 contains terminal ct-D-ribofuranosyluronic groups (19). With this obvious exception, all known glycuronic acids in bacterial polysaccharides are py-ranosidic. 

A number of 3-deoxyglyculosonic acids have been identified. These substances are acid-labile and are decomposed on hydrolysis with acid under normal conditions, and have therefore often escaped detection in the past. The simplest member of this class, 3-deoxy-L- /yccro-pentulosonic acid (26), occurs as terminal groups in the capsular polysaccharide from Klebsiella K38. Pyranosidic 3-deoxy-D-r/ircohexulosonic acid is a component of the Vibrio parahaemolyticus 07 and 012 LPS. The same acid, as )3-py-ranosyl groups, is also present in the extracellular polysaccharide from Azo-tobacter vinelandii. ... 

A 3-deoxyheptulosaric acid has been found in the LPS from Acineto-bacter calcoaceticus NCTC 10305. Another acid of this class, 3-deoxy-o-/yxo-heptulosaric acid ° (30), is a component of a plant polysaccharide. One 4-deoxyhexulosonic acid, of unknown configuration, is known and is a component of the E. coli K3 capsular polysaccharide. "... 

The pyruvic acid may also be linked to vicinal positions. When linked to 0-3 and 0-4 of a D-galactopyranosyl residue (40), the dioxolane ring becomes cw-fused. In the limited number of known examples, the absolute configuration at the acetalic carbon atom is (S), as in 40. There are some examples of tra -fused dioxolane rings, and these are more sensitive to hydrolysis with acid than the others. Thus, pyruvic acid is acetalically linked to 0-3 and 0-4 of an a-L-rhamnopyranosyl residue in the Klebsiella type 72 capsular polysaccharide, to 0-2 and 0-3 of an a-D-galactopyranosyl residue in the Streptococcus pneumoniae type 4 capsular polysaccharide, and to 0-2 and 0-3 of a S-D-glucopyranosyluronic acid residue in the Klebsiella K1 capsular polysaccharide. " In the extracellular polysaccharide from... 

In the cell-wall antigen from Staphylococcus aureus M, taurine is linked as an amide (51) to a 2-acetamido-2-deoxy-D-galactosyluronic residue. l-Threonine and L-glutamic acid are linked as amides to D-glucuronic acid residues in the LPS from Rhodopseudomonas sphaeroides ATCC 17023 and in the capsular polysaccharide from Klebsiella K82, respectively. In the capsular polysaccharide from E. coli K54, L-serine and L-threonine, in the ratio 1 9, are linked to the carboxyl group of a D-glucuronic acid residue. In the capsular polysaccharide from Haemophilus influenzae type d,... 

In some polysaccharides, the reducing terminal is linked, through a phosphoric diester linkage, to O-1 of a 2,3-di-6 -acylglycerol. This structural feature has been demonstrated for some capsular polysaccharides from E. coli and Neisseria species, - but is probably more common than that. Non-covalent linkage between the lipid part and the cell membrane may explain why extracellular polysaccharides often occur as capsules, and the high (apparent) molecular weight observed for these polysaccharides may be due to micelle formation in aqueous solution. 

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