Sialic acids structures

Nam H-J, Gurda-Whitaker B, Gan WY, Ilaria S, McKenna R, Mehta P, Alvarez RA, Agbandje-McKenna M. Identification of the sialic acid structures recognized by minute virus of mice and the role of binding affinity in virulence adaptation. J. Biol. Chem. 2006 281 25670-25677. 

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]. 

The sialic acid structure incorporates a carboxylate at the anomeric centre, which can be inductively electron donating in its deprotonated form and inductively electron withdrawing when protonated, as well as deoxygenation of the position next to the anomeric centre. These features make sialosyl cations more stable than simple aldopyranosyl cations, and hydrolysis and solvolysis reactions have been investigated using the substrates shown in Figure 3.24. 

If possible, typical biological sources have been indicated. In the case of a sialic acid structure being proven by mass spectrometry and/or NMR spectroscopy, reference numbers refer in general to such studies or to review articles including this sialic acid. 

Fig. 19. Model of sialic acid structural features required for the interaction with sialate lyase and binding of inhibitors. Based on data from ref. [892].

The spikes are of two types. One type (haemagglutinin) has a vital role in the first stages of infection, the penetration of host cells. The second type of spike is made of an enzyme called sialidase, whose role is to help newly formed viruses escape from the host cell so that they can move on to infect other cells. As part of this process, sialidase cleaves off sialic acid from oligosaccharides (short chains of carbohydrate units). These sialidase spikes have clefts that contain an acti ve site, into which bound sialic acid (Structure 3.1) fits during the cleavage process. This active site... 

Scheme 17.11 The pH shift induced upon CSS catalysis by release of pyrophosphate, which can be used for colorimetric quantification of enzyme catalysis independent of sialic acid structure.

Reuter, G. Gabius, H.J. Sialic acids structure-analysis-metaboUsm-occurrence-recognition. 

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