Sialidases glycosidic linkage

The aeylneuraminic acids can be released from their glycosidic linkages either by dilute (aqueous or methanolie) acids or sialidases. Special care must be taken in the isolation of the rather labile, O-acv-lated sialic acids, which arc partially non-susceptible to the action of sialidases. Furthennore, in gangliosides, non-O-acetylated sialic acid residues occur, and these are also more or less resistant towards these enzymes. 

Undoubtedly, the most critical area of the sialic acid structure for biological activity is the C-2 centre, which is involved in glycosidic linkages and is substituted with the C-1 carboxylic acid group. 2-Deoxy derivatives are of biological interest [4,103], in particular the 2-deoxy-2,3-didehydro derivatives, which show significant inhibitory activity against sialidases [4,156-158]. 

Exo-a-sialidase (EC 3.2.1.18). Enzyme hydrolyses a-23, a-2,6- and a-2,8-glycosidic linkages of terminal sialic acid residues, Gangliosides, glycotipids, lipofus-cin and lysobisphosphatidic add accumulate in lysosomes of many tissues. Corneal opadties Dementia. No skeletal effects No hepatome y. 

Sialidase inhibitors based on the A-acetylneuraminic acid (NeuSAc) template could include substrate-like, product-like, and transition state-like compounds (reviewed [87]). Sialidase-resistant substrate analogs where the natural oxygen glycosidic linkage is replaced with carbon or sulfur (e.g., 9, 10 [88], Figure 22.4)... 

Table 3. The glycosidic linkage specificity of some sialidases. The rates of reaction for...

New studies have expanded the work of Drzeniek (1972, 1973) with regard to the glycosidic linkage specificity of viral and bacterial sialidases (Corfield et al. 1981 a, b), allowing discrimination between three different viral sialidase activities on the basis of a(2-3) and (2-6) linkages and the nature of the oligosaccharide chain in substrates as described under IV. 3.g). 

The sialidases provide another example of a group of enzymes which show specificity for the type of complex carbohydrate, the nature of the glycosidic linkage (see section IV. 3. h) and the type of sialic acid (sections IV. 3.e) and f). 

While all these enzymes hydrolytically cleave a-glycosidic bonds of sialic acids, another type of sialidase has been discovered, which can also hydrolyze these linkages but preferably forms sialic acid linkages under physiological conditions in the presence of suitable acceptors. These are the /rans-sialidases, occurring in parasites, and a... 

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