Polysaccharide Type III

The numerous examples of regular complex copolysaccharides often involve familiar-looking material for cellulose chemists. Figure 10 shows two pneumococcal polysaccharides. Types III and VIII, also known as "specific soluble substance", which in the 1920 s and early 1930 s were shown to be antigenic although they were free of nitrogen and did not possess any of the properties of peptides. The knowledge achieved by the extensive studies on cellulose and carbohydrates in the first decades of this century was responsible for the early establishment of the chemical structures of Types III and VIII. The revolutionary work on bacterial transformation, in which Avery, MacLeod and McCarty in 1944 identified DNA as the... 

In further studies (Prusansky and Axelrod, 1954) on the same deficiency states discussed above the serum complement was markedly depressed by the intrapeiitoneal injection of pneumococcal polysaccharide type III (Sill) followed 1 hour later by the intravenous injection of a neutralizing amount of specific rabbit antiserum. This depletion process was repeated daily for 3 days. The regeneration of serum complement was followed by determining the serum titer 22 hours after the final injection of rabbit antiserum. The rate of serum complement regeneration by the deficient animals was not significantly different from that of corresponding controls. 

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. 

The arabinogalactans have more frequently been reported for activity in various biological systems. Arabinogalactans are often classified in three groups arabino-4-galactans (Type 1), arabino-3,6-galactans (Type II) and polysaccharides with arabinogalactan side chains (Type III) [14]. The latter type are also called the real pectins [10,11]. Only types I and II will be dealt with in this chapter, as Type III are equal to the pectins discussed below. 

Type III Limit dextrinosis, Forbes or Corl s disease Absence of debranching enzyme Accumulation of a characteristic branched polysaccharide. 

In a recent paper650 the relationships between Rhizobium radicicolum polysaccharides and those of pneumococcus are indicated by crossprecipitin reactions of the former with Types III and VI anti-pneumococcus horse sera. In addition, hydrolysis of the methylated polysaccharide of Rhizobium radicicolum yields equal amounts of 2,3,6-trimethyl-D-glucose, 2,3-dimethyl-D-glucose and 2,3-dimethyl-D-glucuronic acid.65 1 The minimum trisaccharide repeating unit consists, in part, of cello-biuronic acid, and may be represented ... 

Reeves and Goebel72 have shown that hydrolysis of the reduced methylated capsular polysaccharide of Type III pneumococcus yields 2,3,6-trimethyl-D-glucose and the anomeric forms of methyl 2,4-dimethyl-D-glucoside. The cellobiuronic acid units in the polysaccharide are thus linked through position 3 of the D-glucuronic acid residue, probably by /3-D-linkages. That is, the polysaccharide contains alternate 1,3-and l,4-/3-D-linkages. 

Catalytic reduction and methanolysis of the methylated capsular polysaccharide of Type III pneumococcus gives a mixture of methyl 2,3,6-trimethyl- and 2,4-dimethyl-a/3-D-glucopyranosides. The latter, which arises from glucuronic acid units in the polysaccharide, can be separated into crystalline a- and 6-isomers identical with synthetic specimens.84,88... 

Scheme 3 Decasaccharides representing two repeating units of the CBS type III capsular polysaccharide (CBSPIII)...

It was no easy task, consuming years of careful, dedicated work. In a letter to his brother, Avery notes To try to find in that complex mixture, the active principle Try to isolate and identify the particular substance that will by itself when brought into contact with the R cell derived from Type II cause it to elaborate Type III capsular polysaccharide, and to acquire all the aristocratic distinctions of the same specific type of cells as that from which the extract was prepared Some job—full of headaches and heart breaks. But at last perhaps we have it. ... 

Immunoadsorbents can be made with whole antigens or haptens. For example, Haber42 reported the preparation of a Diplococcus pneumoniae Type III immunoadsorbent. The capsular polysaccharide (S III) was p-nitrobenzylated to a low degree of substitution by the method of Avery and Goebel.43 The resultant ether was re-... 

R. E. Reeves and W. F. Goebel, Chemoimmunological studies on the soluble specific substance of pneumococcus. V. The structure of the type III polysaccharide, J. Biol. Chem., 139 (1941) 511-519. 

Tri-O-methyl-D-glucose-(4— 1) 2,3,4-tri-O-methyl-D-glucosiduronic acid Pneumococcus Type III specific polysaccharide B 0 64a... 

Comparison of the activity of sulfated homopolysaccharides such as dextran and cellulose esters with that of neutral homopolysaccharides and sulfated heteropolysaccharides such as heparin and heparan sulfuric acid half esters shows potent virucidal activity against human T-cell lymphotropic virus type III (HTLV-III) for the sulfated homopolysaccharides. In contrast, neutral homopolysaccharides have no effect and sulfated heteropolysaccharides exhibit only a little effect on HTLV-III activities. This suggests that the sulfate moiety and the type of polysaccharide are most important in inhibiting growth of HTLV-III [126]. 

Fig. 4.—Proposed Conformation of the Repeating Unit of the Type III Polysaccharide Antigen of Group B Streptococcus.

For most antigens, the production of antibody (immunoglobulin) is based on the cooperative interaction of two types of lymphocyte, called T-cells (thymus-derived) and B-cells (bone marrow-derived). The T-cells, preprimed with macrophage-presented antigen, stimulate the B-cells to secrete copious quantities of antibody. However, on the basis of animal studies, such polysaccharide antigens as the type III pneumococcal polysaccharide have been considered to be T-cell-independent, as they are capable of triggering B-cells to produce antibody (IgM) in T-cell-deficient mice.167 These studies also indicated... 

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