Chemical synthesis of α-sialoside is one of the most difficult subjects in the field of carbohydrate chemistry due to its characteristic 3-deoxy and 2-carboxylated structure. In this review, we outline the footsteps of the sialoside chemistry to the surmounting of the synthetic disadvantages and highlight a recently reported novel sialyl donor, N-Troc-protected sialic acid derivative.

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Polysialic acid (PSA) is a versatile biopolymer. PSA can be detected in a wide range of eukaryotes, including higher invertebrates and vertebrates, and also some prokaryotes, such as the neuroinvasive bacteria Neisseria meningitidis B. In mammals, PSA expression is developmentally regulated and plays significant roles in both neural development and in cancer. In bacteria, PSA is responsible for virulence. Spectroscopic methods, combined with immunological analysis, have played a significant role in understanding the relationship between PSA's structure and its biological functions. Chemical tools, including unnatural sialic acid analogs, have facilitated modulation of PSA's structure in cell culture and in vivo. The use of unnatural sialic acids has led to the development of vaccines for meningitis and cancer.

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In the vertebrate nervous system polysialic acid (PSA) has been identified as a carbohydrate portion of neural cell adhesion molecule (NCAM). PSA is principally expressed in the embryonic and early postnatal brain, and has important functions in neuronal development. However, distinct populations of PSA-expressing cells are present in two exceptional regions of the adult brain: the hippocampus and subventricular zone of the forebrain where neurogenesis continues into adulthood. The accumulating evidence has shown that the PSA-expressing immature neurons in the two adult neurogenic regions are different from mature neurons in morphological, biochemical and electrophysiological properties. Here we describe the nature of PSA-expressing immature neurons in the adult neurogenesis and discuss the function of PSA in the adult neurogenesis.

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Sialic acids are commonly present as monosialyl residues at the non-reducing terminal end of glycoconjugates. In some cases, α2→8 linked di/oligosialic acid chains with DP 2 or 3 sialic acid residues are common structural units of gangliosides, and involved in various biological processes, such as cell adhesion, cell differentiation, signal transduction, and surface expression of stage specific antigen. In contrast, little attention has been paid to the occurrence and functions of such short sialyl di/oligomers on glycoproteins, while polysialic acid (DP≥8) in embryonic NCAM has been extensively studied as a regulator of cell adhesion in neurogenesis. As analytical methods to detect di/oligosialic acid structures have been improved, several glycoproteins containing di/oligo/polysialic acid chains have been identified. It is thus hypothesized that these di/oligosialic acid residues on glycoproteins may have similar important functions in common with those proposed for the gangliosides or may have new functions. Currently, several studies showing the importance of di/oligosialic acid-containing glycoproteins have emerged. In this review, recent advances in such studies of di/oligosialic acid residues on glycoproteins, including analytical methods, occurrence, biosynthetic pathways, and functions, are described.

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So far, twenty members of the mouse sialyltransferase family have been identified. Among them, the cDNA cloning of a second type of β-galactoside α2, 6-sialyltransferase (ST6Gal II) and a sixth type of α2, 8-sialyltransferase (ST8Sia VI) has been performed most recently. ST6Gal II is a counterpart of ST6Gal I, and the ST6Gal II gene has a similar genomic structure to the ST6Gal II gene. But unlike ST6Gal I, which exhibits broad substrate specificity toward oligosaccharides, glycoproteins, and glycolipids, ST6Gal II exhibited limited substrate specificity toward some oligosaccharides and glycoproteins, all of which have the Galβ1, 4GlcNAc sequence at the nonreducing end of their carbohydrate groups. The expression pattern of the ST6Gal II gene was also different from that of the ST6Gal I gene. Another enzyme, ST8Sia VI, exhibited broad substrate specificity toward glycoproteins, glycolipids, and sialyloligosaccharides, all of which have the NeuAcα2, 3(6)Gal sequence at the nonreducing end of their carbohydrate groups. For glycoproteins, ST8Sia VI prefered O-glycans to N-glycans as acceptor substrates. In addition, ST8Sia VI also exhibited higher activity toward O-glycans than glycolipids. It has been shown that ST8Sia VI is the first mammalian α2, 8-sialyltransferase that sialylates O-glycans preferentially.

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Cells of the innate immune system such as mononuclear phagocytes express a wide range of surface receptors that mediate recognition events involving both the host and the pathogen. Many of these are lectin-like receptors that interact with carbohydrate ligands. The CD33-related sialic acid binding Ig-like lectins (siglecs) are recently discovered receptors of the innate immune system that are specialised for sialic acid recognition at the cell surface and which contain tyrosine-based signalling motifs in their intracellular domains. There are significant differences in the repertoire of CD33-related siglecs amongst mammalian species, reflecting rapid and ongoing evolution of the genes encoding these proteins. Despite these differences, the overall expression patterns on leucocyte subsets within the innate immune system are very similar, indicating a conserved role for these receptors in regulating innate immune responses. Detailed studies with different glycans have revealed unique as well as overlapping carbohydrate binding specificities of each siglec. However, all CD33-related siglecs are normally masked via cis-interactions with sialic acids at the cell surface and this is likely to modulate trans interactions with ligands expressed on other cells. Some pathogens such as Neisseria meningitidis can also express sialic acid, and recent studies indicate that pathogen-associated sialic acids can also function as ligands for siglecs and enhance the interactions of pathogens with cells of the innate immune system. It is currently unknown whether these these interactions benefit the host, the pathogen or neither.

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