Zwitterionic Polysaccharide

Zwitterionic polysaccharides are candidate immunotherapeutic agents [140, 141] that can activate immune responses dependent on a major histocompatibility complex class II (MHCII)-mediated T cell in the absence of protein [142], Polysaccharide 

SCHEME 14.13 Synthesis of the SCWP fragment from Bacillus anthracis by Boons and coworkers. Fmoc, 9-fluorenylmethoxycarbonyl TDS, dimethylthexylsilyl. 

SCHEME 14.14 Synthesis of PS A1 repeating tetrasaccharide unit from Bacteroides fragilis by Seeberger and coworkers. DMTST, dimethyl(methylthio)sulfonium triflate TTBP, 2,4,6-tri-terf-butylpyrimidine. 

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While most polysaccharide antigens act in a T-cell independent fashion, zwitterionic polysaccharides have been shown to induce T-cell mediated immunity [358]. Several bacteria produce zwitterionic CPS, which contain both free amine and free carboxyl groups in the repeating unit. These include CPS types 5 and 8 of Staphylococcus aureus, PSA from B. frag-ilis and the type 1 S. pneumoniae polysaccharide (O Fig. 28). Vaccination with zwitterionic polysaccharides have been shown to produce T-cell mediated immunity in mice [359], and vaccines based on zwitterionic CPS may be useful for combating several common bacterial pathogens. 

Figure 6.3 Zwitterionic polysaccharide conjugation to a carbohydrate antigen.

Tzianabos AO, Wang JY, Kaspar DL (2003) Biological chemistry of immunomodulation by zwitterionic polysaccharides. Carbohydr Res 338 2531-2538... 

The Databases menu provides tools for building polypeptides (Amino Acids, Make Zwitterion, Sequence Editor), polynucleotides (Nucleic Acids), polysaccharides (Saccharides), and organic polymers (Polymers) from residues (monomer units) as exemplified for DNA in Figure 14.11. 

Protein molecules fall within the limits of colloidal dimensions and are therefore subject to the same interfacial forces as polysaccharides. They too are amphilphilic—existing as zwitterions (internal salts) in water at neutral pH and in the solid state, and reacting chemically and physically with ionic and some nonionic molecules, often specifically (Hart et al., 1992). Their complexes have different bond strengths along with possibly different conformations (Dickinson and Euston, 1991a, b Mackie et al., 1991). 

An example of the use of a post-glycosylation oxidation strategy is presented by the recent synthesis of monomeric and dimeric repeats of the zwitterionic Type 1 capsular polysaccharide from Streptococcus pneumonia (Spl) depicted in... 

Wu X, Cui L, Lipinski T, Bundle DR (2010) Synthesis of monomeric and dimeric repeating units of zwitterionic type 1 capsular polysaccharide from Streptococcus pneumonia. Chem Eur J 16 3476-3488... 

Amphoteric polysaccharides are, perhaps, the most chemically sophisticated polysaccharides, which may explain the reluctance of formulators to explore them. Depending on the pH of a cosmetic formulation, the amphoteric polysaccharide can be cationic, anionic, or both i.e., it can be a quasi-nonionic species or zwitterionic (Fig. 40). A zwitterion is a molecular species wherein a proton from the acidic portion of the amphoteric resides on the basic. The resulting molecule has positive and negative charges in close proximity, effectively canceling one another and leaving the polysaccharide nonionic overall. 

Amphoteric polysaccharides are challenging to formulate they can be soluble when cationic or anionic, but insoluble in their zwitterionic form. These polyglycans can also have complex chemistries in the presence of salts and surfactants. Salts can modify the pH at which amphoteric polymers become zwitterionic. Surfactant behavior is more complex. When the amphoteric polymer is cationic, it is incompatible with anionic surfactants... 

Bundle et al. described the synthesis of di-, tri and hexameric repeating units of the same zwitterionic Spl capsular polysaccharide from Stepto-coccus pneumonia following an approach of conventional glycosylation to avoid the poorly reactive uronic acid derived glycosyl donors and... 

In Reference 71, a CE method for the chiral separation and quantitation of zwitterionic cetirizine (CTZ) and hydroxyzine (HZ) was developed. Maltodextrin, a linear polysaccharide, was applied as CS. An uncoated 75- JLm-i.d., fused-silica capillary of 60 cm (50 cm effective length)... 

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