Modification of N-acetylneuraminic acid

Suttajit, M., and Winzler, R., 1971, Effect of modification of N-acetylneuraminic acid on the binding of glycoproteins to influenza virus and on susceptibility to cleavage by neuraminidase, J. Biol. Chem. 246 3398-3404. 

Ebert, W., Metz, J., and Roelcke, D., 1972, Modifications of N-acetylneuraminic acid and their influence on the antigen activity of erythrocyte glycoproteins, Eur. J. Biochem. 21 410. 

Aldiough it is clear diat a modification at die S-N position of N-acetylneuraminic acid influences reactivity and stereoselectivity in glycosylation reactions, a universal S-N protecting group that would address all the challenges of sialylation has not yet emerged. 

Synthetic studies for sialic acid and its modifications have extensively used the catabolic enzyme N-acetylneuraminic acid aldolase (NeuA E.C. 4.1.3.3), which catalyzes the reversible addition of pyruvate (70) to N-acetyl-D-mannosamine (ManNAc, 11) to form the parent sialic acid N-acetylneuraminic acid (NeuSNAc, 12 Scheme 2.2.5.23) [1, 2, 45]. In contrast, the N-acetylneuraminic acid synthase (NeuS E.C. 4.1.3.19) has practically been ignored, although it holds considerable synthetic potential in that the enzyme utilizes phosphoenolpyruvate (PEP, 71) as a preformed enol nucleophile from which release of inorganic phosphate during... 

Chemical modification e.g. periodate oxidation and then reduction) or loss of the terminal N-acetylneuraminic acid residues of human-plasma a,-antitrypsin did not destroy its ability to inhibit either trypsin or chymotrypsin neither did oxidation of the exposed D-galactopyranosyl residues in the desialylated glycoprotein with D-galactose oxidase. However, enzymic oxidation of the D-galactopyranosyl residues increased the survival time of the modified glycoprotein in plasma towards that exhibited by fully sialylated a -antitrypsin, whereas the desialylated glycoprotein was rapidly cleared following injection into rats. Contrary to previous evidence, there appears to be little or no difference between the carbohydrate compositions of the M and Z variants of human-plasma a,-antitrypsin. ... 

The 5-N-acetyl group of CMP-A -acetylneuraminic acid can be modified by a hydroxylase to form CMP-7V-glycolyl-neuraminic acid. The enzyme occurs in many non-human tissues and has been cloned from several species [113]. JV-Glycolyl-neuraminic acid can then be transferred by sialyltransferases to glycoproteins and mucins, resulting in a sialic acid modification which is common in manunalians but in humans is antigenic, and only found in exceptional conditions such as in cancer (5). 

---