Sialic-acid-recognizing proteins

Extensive research has focused on the synthesis of structurally modified sialic acid derivatives and sialylmimetics as probes or potential inhibitors of specific sialic acid-recognizing proteins, and several comprehensive overviews have been published [26, 30-34], An underlying theme in efforts directed toward the development of novel sialic acid derivatives as biological probes is the complexity of the chemical manipulations associated with sialic acids [30, 32], The chemical strategies and conditions for sialylation are discussed in Chapter 5. 

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 ability of viruses to infect specific cell types is dictated in part by the ability of these viruses to bind to particular structures or receptors on the surfaces of cells. In some cases, these receptors are carbohydrates. For example, influenza virus recognizes sialic acid residues present on cell-surface glycoproteins. The viral protein that binds to these sugars is called hemasslutinin(Fisure 11.31). 

The influenza virus is one of the most extensively studied vimses at present. The influenza virus recognizes sialic acid on the host cell surface, followed by infection and transmission [109]. Two spike-formed proteins (hemagglutinin and neuraminidase) are found on the surface of the influenza virus [110,111]. Hemagglutinin binds to the host cells through recognizing the ligand containing sialic acid on the surface of infected cells, while neuraminidase eliminates sialic acid from the cell surface to avoid inhibition of the transmission of newly formed virus particles. 

Figure 6.6 Statistically distributed sialic acid on the polar surface of polymeric mono-layers is recognized by the viral lectin called hemagglutinin (compare with Con A, Figures 4.11 and 4.12). A protein surface layer is formed, which disturbs the order in the polymeric monolayer below. Colorimetric measurements of the colour change from blue to red allow quantitative determination of the protein concentration.

Because of the destabilizing effect of the mutations on the structure of the mutant proteins, the NA mutant and some of the HA mutants display a marked thermo-lability. The NA mutant loses both enzyme activity as well as reactivity to the NC-10 mAb, which only recognizes the native NA (7). The HA mutants lose the ability to bind to the receptor on red blood cells, resulting in a decrease in the hemagglutination titer, or to the sialic acids on fetuin in a fetuin-based ELISA assay. 

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