Glycosidically Linked Sialic Acids

Polysialic acid, a homopolymer of a2,8-glycosidically linked sialic acid residues, is a major regulator of cell-ceU interactions in the developing nervous system and a key factor in maintaining neural plasticity and exerts different glycopattems in the brain regarding the time scale during brain development. ... 

Glycosidically Linked Sialic Acids a) The Type of Sialic Acid... 

It may be clear that this NMR method can generally be applied for the determination of the number and positions of 0-acetyl groups in glycosidically linked sialic acids, occurring in oligosaccharides or glycopeptides derived from glycoconjugates. 

Table 3. H NMR chemical shift data, useful for discrimination between ol- and p-glycosidically linked sialic acids (Haverkamp et al 1978, 1982)...

The sialidases cleave a-glycosidically linked sialic acid residues (Gottschalk 1958, Kuhn and Brossmer 1958). The sialic acids occurring in nature are found in the a-glycosidic conformation (see chapter B) with the exception of CMP-Neu5Ac which is a -glycoside (Haverkamp et al 1979 b) and which is not a substrate for sialidases. 

Long term hormonal control functions in the expression of enzyme concentrations and de novo acceptor molecule synthesis in the case of sialyltransfer reactions. Examples in development have been cited (sections II.2, II. 3, and III. 10), and the regenerating liver has proved valuable in studies of this kind, e.g. UDP-GlcNAc 2-epimerase (Okubu et al. 1976, Okamoto and Akamatsu 1980). Elevation of enzyme concentration could be shown to be a function of de novo protein synthesis. Study of hormone effects (oestrogen, progesterone) on sialyltransferase activity and glycosidically linked sialic acid levels in the cervical cyclic phenomena have been reported (Moghissi and Syner 1976, Chantler and Debruyn 1977, Hatcher et al. 1977, Nasir-ud-Din et al. 1979, Wolf et al. 1980). Similar effects have been demonstrated in rat endometrium (Nelson et al. 1975). 

The Trypanosoma cruzi trani-sialidase catalyzes the reversible transfer of NeuAc from a NeuAc-a-2,3-Gal-)8-OR sequence to an acceptor hearing the Gal-)8-OR motif (Scheme 42) [54], The enzyme is a particularly useful sialidase because it has very little hydrolytic activity and tends to almost exclusively catalyze transsialylation to a galactose. However a major drawback to this method is that to drive the gly-cosylation to completion, there is a need for large quantities of complex a-2,3-linked sialyl donors, which are generally difficult to obtain from natural sources. Other natural donors with a-2,6- or a-2,8-linked sialic acids have been examined but were discovered to be poor sialyl donors for a-2,3-sialylations catalyzed by T. cruzi trans-sialidase [55]. Simple aryl a-sialosides, such as the 4-nitrophenyl glycoside 122 and methylumbelliferone glycoside 130 (Scheme 43), have been found to be excellent... 

In contrast to fliese hansmolecular TSs, the group of Yu-Teh Li described an intramoleeular TS in die leech that forms 2,7-anhydro-Neu5Ac upon release of siahc acid fiom die glycosidic linkage. Such an enzyme ( neuraminidase B ) was found in Streptococcus pneumoniae by Gut et al This enzyme has a strict specificity for a-(2 3)-linked sialic acid substrates. 

Sialic acids are a family of 3-deoxy-2-ulosonic acids found most frequently as a-glycosidically linked terminal residues of glycoproteins and glycolipids. The most abundant sialic acid is N-acetylneuraminic acid (5-acetamido-3,5-di-deoxy-D-glycero-D-galacto-nonu osonic acid, NeuSAc, 1), which was first isolated in the 1930s. To date, 36 sialic acids have been isolated, many of which are 0-acetylated derivatives of N-acylated neuraminic acid [1]. 

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