Sialylation with Modified Donor and Acceptor Substrates

Sialylation with Modified Donor and Acceptor Substrates 

In transferase-catalyzed reactions, the activated neuraminic acid serves as precursor for the introduction of the terminal NeuSAc residue into various oligosaccharides. This approach is particularly attractive because the chemical synthesis with NeuSAc glycosyl donors has two drawbacks the low yielding glycosylation reaction and the formation of anomeric mixtures. 

CMP-neuraminic acid can be used in oligosaccharide synthesis as a substrate for various a2-6-sialyltransferases isolated from rat liver [50] or bovine colostrum [51] as well as a2-3-sialyltransferases isolated from porcine liver [52] and porcine submaxillary glands [53]. Recently, the enzyme has been overexpressed in a baculovirus system [54]. 

Following the enzymatic synthesis of CMP-Neu5Ac, isolated a2-6-sialyl-transferases could be used to introduce sialic acid to the N-acetyl lactosamine derivates a-f in position 6. This afforded a series of trisaccharide derivates Neu5Aca2-6 Gal l-4GlcNAc l-R. The unblocked trisaccharide a [55], the methyl glycoside b [56], the -Asn derivative c [57], the pentapeptide derivative d [58], the allyl e [59], and the pent-4-enyl glycoside f [48] can be prepared in convincing yields (Fig. 6). 

Some sialyltransferases recognize modified CMP-Neu5Ac such as those in which the hydroxyl group at C-9 is replaced with an amido, fluoro, azido, acetamido, or benzamido group [60-63]. Acceptor analogs in which the aceta-mido function is replaced by an azide, phthalimide, carbamate, or pivaloyl functionality are also accepted by the enzyme [64]. 

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