Sialic acids proton

In addition to binding to sialic acid residues of the carbohydrate side chains of cellular proteins that the virus exploits as receptors, hemagglutinin has a second function in the infection of host cells. Viruses, bound to the plasma membrane via their membrane receptors, are taken into the cells by endocytosis. Proton pumps in the membrane of endocytic vesicles that now contain the bound viruses cause an accumulation of protons and a consequent lowering of the pH inside the vesicles. The acidic pH (below pH 6) allows hemagglutinin to fulfill its second role, namely, to act as a membrane fusogen by inducing the fusion of the viral envelope membrane with the membrane of the endosome. This expels the viral RNA into the cytoplasm, where it can begin to replicate. 

Sialin was first identified as the product of the gene defective in sialidosis, a lysosomal storage disorder. The transporter mediates the movement of sialic acid out of lysosomes by coupling to the proton electrochemical gradient across the lysosomal membrane. Unlike the vesicular neurotransmitter transporters which are antiporters, sialin is a sympoiter with sialic acid and protons both moving out of the lysosome. 

A New Approach to Sialic Acid Glycosides. One of the key steps in our synthesis of NeuSAc was the addition of methanol to 10. The furan presumably stabilizes the cation formed by protonation of the [3-carbon of the glycal. Indeed, as discussed at the outset, the de facto nucleophilic character of the furan was one feature which recommended its use. 

N. K. Sauter, M. D. Bednarski, B. A. Wurzburg, J. E. Hanson, G. M. Whitesides, J. J. Skehel, and D. C. Wiley, Hemagglutinins from two influenza virus variants bind to sialic acid derivatives with millimolar dissociation constants A 500-MHz proton nuclear magnetic resonance study, Biochemistry, 28 (1989) 8388-8396. 

Glucuronic acid and sialic acid are normally present in conjugated forms. After degradation of these components in lysosomes, the free monosaccharides are released by a specific membrane transport system. The lysosomal sialic acid transporter from rat liver has been purified to apparent homogeneity in a reconstitutively active form. The transporter recognized structurally different types of acidic monosaccharides such as sialic acid, glucuronic acid, and iduronic acid. The transport was proton gradient dependent, and saturable with a of approximately 0.4mM [211]. 

L. Poppe and H. van Halbeek, Nuclear magnetic resonance of hydroxyl and amido protons of oligosaccharides in aqueous solution. Evidence for a strong intramolecular hydrogen bond in sialic acid residues, J. Am. Chem. Soc., 113 (1991) 363-365. 

The first question concerns the nature and relative proportions of constituent monosaccharides. In principle, this is obtained by acidic hydrolysis (Biermann 1988) but, in practice, it must be carefully applied as there are a certain number of important specific cases. Hydrochloric, sulfuric, and trifluoroacetic acids are used whose 1 N solutions have a pH of 0.1, 0.3, and 0.7, respectively. When hydrolysis liberates monosaccharides fragile in an acidic medium, a delicate balance between the risk of incomplete hydrolysis and partial destruction of the hydrolysis product must be maintained. The fragile sugars are pentoses, deoxy sugars, and uronic and aldonic acids. When sialic acid is kept for 30 min at 90°C in 0.01 M HCl, 20% decomposition occurs. With neutral polysaccharides, decomposition can be limited to less than 9%. The acetyl groups of acetamides are hydrolysed and relatively stable protonated amino sugars are obtained. 

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. 

Free as well as glycosidically bound sialic acid give rise to highly characteristic H NMR parameters. The H NMR spectra are generally recorded in D2O, and because of the pH dependency of the proton chemical shifts, the spectral data are standardized at pD 6-7. The choice of the pH is also of importance in view of the earlier discussed de-O-acylation, 0-acyl migration, and autohydrolysis. 

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