Sialic acids nucleotide derivatives

The final step in the activation of sialic acid to a nucleotide sugar occurs by the reaction shown above. It is clear that this reaction is unique in the sense that (1) the monosaccharide itself is the substrate rather than the more common 1-phosphate, and (2) the nucleotide sugar contains only one phosphate group rather than two. Like several of the other enzymes participating in sialic acid biosynthesis, CMP-sialic acid synthetase can utilize the N-glycolyl as well as the N-acetyl derivative. 

Since none of these enzymes have been extensively purified, they are differentiated from one another primarily by the nature of the acceptor and by the linkage synthesized. TTie general reaction catalyzed by the sialyl-transferases is shown in Fig. 9. Although at least four different sialic acids have been described (Gottschalk, 1960a), only two nucleotide sugar derivatives have been isolated, namely, CMP-2V-acetylneuraminic acid and CMP-N-glycolylneuraminic acid it is presently not known whether different enzymes catalyze the transfer of these two different N-acylneu-raminic acids and most of the sialyltransferase literature is limited to the more readily available CMP-N-acetylneuraminic acid. 

The procedure consists of stepwise enzymatic degradation of chemically prepared neuraminic acid derivatives (3) to give the corresponding modified ManNAc analogs (1), which is followed by subsequent neuraminic acid reconstruction in the presence of [3- C] labeled pyruvate (21). To ensure complete conversion in the desired direction the first step was promoted by cofactor-dependent reduction of pyruvate the second, synthetic step, was uncoupled by destruction of the nucleotide cofactor before addition of labeled pyruvate. Sialic acids such as 20 with high label incorporation (> 87%) were obtained in good yields (46-76%). 

Application of strategy B also made accessible nucleotide monophosphosialic acid derivatives with the cytidine replaced by other pyrimidine and purine bases, although in modest overall yields only [55]. By following pathway B a CMP- disialyl derivative could be synthesized. This compound has a second sialic acid unit a-linked to the 8-OH group of the CMP-activated sialic acid [56]. 

Wolf et al. reported the synthesis of cytidine-5 -monophosphate-sialic acid derivatives (70). The synthesis involves the reaction of cyclo-Sal-nucleotides with different phosphate nucleophiles. Cyc/o-Sal-nucleotides were also used to prepare monophosphate-linked sugar nucleotides in high yields. These compounds were used for enzymatic studies (bacterial polysialyltransferase) and the enzyme showed marked differences in utilising these compounds. 

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