Glycoconjugates sialic acid-terminated

As terminal constituents of glycoconjugates, sialic acids are involved in a wide range of biological phenomena. Different approaches and strategies have been developed to improve yield and stereoselectivity in sialylation reactions. Recently it has been reported that a substituent at the C-5 amino group in sialic acid influences the reactivity of both sialyl donors and acceptors. This review sununarizes the latest accomplishments in sialylations using different N-substitued sialyl derivatives. 

Both hemagglutinin and sialidase are carbohydrate-recognizing proteins and in humans recognize the well-known sialic acid, A-acetylneuraminic acid (Neu5Ac, 3), associated as the terminal carbohydrate unit of upper respiratory tract and lung-associated glycoconjugates.12,14... 

The NA (EC 3.2.1.18) catdyses the hydrolysis of the a-(2,3) and a-(2,6) glycosidic linkage between a terminal sialic acid and its adjacent carbohydrate moiety on a variety of glycoconjugates. 

Due to its high efficiency, the one-pot three-enzyme approach described above should also be suitable for direct transferring modified sialic acid residues to glycoconjugates containing a terminal Gal or GalNAc residue. 

Whereas for a long time the main function of terminal sialic acid residues was considered as a mask for recognition sites on cell surfaces, e.g. galactose residues or antigens as outlined above, it is only in the last few years that receptors have been described which connect the structural diversity of sialylated glycoconjugates to specific functions in cellular interactions. 

Influenza virus sialidase recognizes and cleaves terminal a-ketosidically linked sialic acids from glycoconjugates, and is therefore termed an evo-glycohydrolase [20-22]. The role of the sialidase in the infective life cycle of influenza virus appears varied and includes functions such as promoting the release of the viral progeny from the host... 

Viral NA is an exoglycosidase that hydrolyses terminal sialic acid residues from any glycoconjugate, including the viral glycoproteins themselves. The virion NA spikes are tetramers of the NA molecules that are anchored in the lipid bilayer by an amino-terminal hydrophobic amino acid sequence. Unlike HA, NA does not undergo post-translational proteolytic processing, and the NA spikes are distributed asymmetrically on the surfaces of the progeny virions. 

Sialyltransferases. In eukaryotic cells, addition of terminal sialic acid to glycoconjugates is carried out by specific enzymes called sialyltransferases (STs). STs catalyze the transfer of a sialic acid from the activated nucleotide sugar donor CMP-N-acelylneuraminic acid (CMP-NeuSAc) to the terminal nonreducing position of oligosaccharide chains either of glycoproteins or glycolipids. 

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