176 Sialic acid complexes

The observation of high levels of free sialic acid in lipid extracts of WgaKI1 and WgaRVIII cells prompted us to examine whether it might be sialic acid complexed with the nucleotide cy-tidine monophosphate (i.e. CMP-sialic acid). 

This family contains non-enveloped DNA viruses that bind to their receptors via interactions with the distal knob of the penton fibers attached to the vertices of the icosahedral virions. Human adenoviruses mainly cause respiratory and gastrointestinal infections. Several adenoviruses also infect the eye where the most important disease is epidemic keratoconjunctivitis (EKC), caused primarily by Ad8, Adl9, and Ad37. Ad37 binds preferentially to a2-3-linked sialic acid which is the most frequent type of sialic acid linkage in corneal and conjunctival cells [201]. The crystal structure of the Ad37 knob-sialic acid complex has been elucidated [202]. 

The carbohydrate has sites for ionic interaction (clusters of sialic acid or sulphate residues) and also hydrophobic interaction (clusters of hydrophobic methyl groups offered by fucose residues). Sedimentation velocity has been a valuable tool in the selection of appropriate mucoadhesives and in the characterisation of the complexes [ 138-143]. 

B neuraminidase and its complex with sialic acid. Embo J 11 49-56 Burmeister WP, Henrissat B, Bosso C, Cusack S, Ruigrok RW (1993) Influenza B virus neuraminidase can synthesize its own inhibitor. Structure 1 19-26 Calfee DP, Hayden FG (1998) New approaches to influenza chemotherapy neuraminidase inhibitors, Drugs 56 537-553... 

Varghese IN, Colman PM (1991) Three-dimensional structure of the neuraminidase of influenza virus A/Tokyo/3/67 at 2.2 A resolution. 1 Mol Biol 221 473 86 Varghese IN, Laver WG, Colman PM (1983) Structure of the influenza virus glycoprotein antigen neuraminidase at 2.9 A resolution. Nature 303 35 0 Varghese IN, McKimm-Breschkin IL, Caldwell IB, Kortt AA, Colman PM (1992) The structure of the complex between influenza virus neuraminidase and sialic acid, the viral receptor. Proteins 14 327-332... 

Figure 1.35 The complex structure of an asparagine-linked polysaccharide. Note the branched nature of polymer with terminal sialic acid residues on each chain. 

Fig. 15.3 Plant and mammalian N-glycans have different structures. As illustrated here, a core structure (in gray) is common to plant and mammalian biantennary complex N-glycans. However, differences in the glycan processing machineries in plants and in mammals result in the absence of sialic acids in the terminal position of the antennae and the presence of a bisecting p (1,2) -xylose and of an a(l,3)-fucose residue in PMPs instead of the a(l,6)-fucose linked to the proximal N-acetylglucos-amine of native mammalian N-glycans.

FIGURE 3-3 Structure of some simple sphingolipids. X may be a complex polysaccharide either containing sialic acid (gangliosides) or not (globosides). See also Figures 3-4 and 3-9 for the nomenclature and structure of some of the complex brain sphingolipids. 

Gal/GalNAc or Man/GlcNAc, there are also receptors (e.g., the macrophage sialic acid receptor) for the recognition of sialylated complex glycans.10... 

C5-derived peptide in serum. This molecule lacks anaphylatoxin activity (i.e. it cannot cause smooth muscle contraction), and its ability to cause che-motaxis in neutrophils is about 10-20 times lower than that of C5a. However, human serum also contains a heat-stable, anionic protein termed co-chemotaxin (relative molecular mass = 60 kDa), which acts in a concentration-dependent manner to permit C5a des Arg to act as a chemoattractant for neutrophils. Thus, C5a des Arg plus cochemotaxin working together probably account for most of the neutrophil chemoattractant activity in vivo following complement activation. The mechanism of action of cochemotaxin is unknown, but it may form a physical complex by attaching to a sialic acid residue on the oligosaccharide chain of C5a des Arg. Deglycosylation of C5a des Arg increases its chemoattractant activity more than 10-fold, and its dependency upon cochemotaxin is decreased. 

Figure 12.15 Gangliosides. The prefix mono-, di, tri- or tetra- denotes the number of sialic acid W-acetyl neuraminic acid, NANA) residues present in the molecule. The many different gangliosides have complex structures and for convenience shorthand notations are used. The two commonest were introduced by Svennerholm, who named the parent compound GM1, and Wiegnandt, who named it Ggnti. The latter system gives enough information for the structures to be worked out from the shorthand form once the symbols have been learnt. GalNAc represents N-acetyl galactosamine in the above structure.

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