Sialic acid effects

Selenoglycosides of sialic acid have been successfully prepared in excellent yields from the corresponding peracetylated glycosyl chloride with phenylselenol in the presence of N,N-di-isopropylethylamine [519]. This reagent combination succeeded where others were less effective or failed (Scheme 4.98 [520]. 

Gyorgy, P., Jeanloz, R. W., von Nicolai, H., and Zilliken, F. (1974). Undialyzable growth factors for Lactobacillus bifidus var. pennsylvanicus. Protective effect of sialic acid bound to glycoproteins and oligosaccharides against bacterial degradation. Eur. J. Biochem. 43,29-33. 

Host cell mimicry Sialic acid is part of the glycocalyx of many host cells. The coat of some bacteria contain sialic acid which may reduce the effectiveness of the response of the immune system to the foreign nature of the coat. 

Example 5 Hayakawa and Noyori group in their studies on new activators for phosphoroamidite coupling reactions have applied the most effective member of the group of acid/azole complexes AT-(phenyl)imidazolium tri-flate (N-PhIMT) in the efficient synthesis of biologically important compounds [20j]. A noteworthy example is synthesis of cytidine-5 -monophos-pho-AT-acetylneuraminic acid. This compound is a source of sialic acid in the sialyltransferase-catalysed biosynthesis of sialyl oligosaccharides [25]. 

H Shiono, A Shibukawa, Y Kuroda, T Nakagawa. Effect of sialic acid residues of human ay-acid glycoprotein on stereoselectivity in basic drug-protein binding. Chirality 9 291-296, 1997. 

This cooperative effect of several ligands at the surface of a liposome was recently demonstrated by the inhibition of agglutination of erythrocytes (natural vesicles covered with sialic acids) with the influenza virus by means of sialyl gangliosides. The lowest concentration of sialyl derivatives required for the inhibition was found to be 10 pM in solution whereas it was 20 nM at the surface of a vesicle. Actually, arrays of sialic acid at the surface of liposomes were found to be moderately more effective than sialic acid groups linked to a soluble polymer but as good or better than the best known naturd inhibitors of hemagglutination (i.e. mucins and macroglobulins) [150]. 

Table I summarizes the inhibitory effect of CMP and enzymatically digested CMP on the morphological change of CT-treated CHO-Kl cells. At 20 p l, CMP effectively suppressed the CT-induced morphological change of CHOKl cells. Removal of sMc acid resulted in the complete loss of inhibitory activity. The results imply that the sialic acid moieties of CMP are essential for inhibition. The inhibitory activity remained to a small extent even after hydrolysis of CMP with pronase. Therefore, it seems that not only sialic acids residues but also the peptide portion of CMP contribute to the inhibition of morphological changes of CHOKl cells induced by CT.

Several CMP conjugates made available by this procedure could be transferred effectively to N-acetyl-lactosamine as an acceptor by using the a-2,6-sialyltrans-ferase from rat liver (Fig. 2.2.5.4). In this manner, several trisaccharides 74-77 could be generated carrying natural as well as non-natural sialic acids in good yields [47], limited so far only by the high cost of the commercial glycosyltransferase. 

Exact analysis of sialic acid is required in biologieal experiments where the biological role of sialic acid is frequently studied with the aid of sialidases, and the amount of sialic acids released is determined. This is also important for periodate oxidation studies on biological systems, where modification of sialic acids by periodate is only assumed, but chemical analysis of this effect by isolation and analysis of the modified sialic acids is seldom performed. These uncertainties in determinations of sialic acid can be overcome by the purification procedures already described. Furthermore, it must be stressed that unequivocal determination of the structure of a sialic acid, especially... 

Radioactive acetate is a cheaper, readily available precursor for experiments on the labelling of sialic acid in tissues or cells, and it effectively labels the N- and O-acyl groups of sialic acids.228 This method is of great value not only for the preparation of radioactive sialic acids having high specific radioactivity but also for metabolic studies of sialic acids. However, the sialic acids must be isolated before determination of the specific radioactivity, as other aeetylated hexosamines are also labelled. 

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