Carbohydrate host receptors

The examples discussed above impressively show the diversity and importance of interaction between bacterial adhesion determinants and carbohydrate-containing receptor molecules. Pathogenic bacteria use binding to carbohydrates in different disease stages. However, many questions remain to be answered to unravel the full spectrum of bacteria-host interactions via carbohydrate binding. 

In addition to binding to sialic acid residues of the carbohydrate side chains of cellular proteins that the virus exploits as receptors, hemagglutinin has a second function in the infection of host cells. Viruses, bound to the plasma membrane via their membrane receptors, are taken into the cells by endocytosis. Proton pumps in the membrane of endocytic vesicles that now contain the bound viruses cause an accumulation of protons and a consequent lowering of the pH inside the vesicles. The acidic pH (below pH 6) allows hemagglutinin to fulfill its second role, namely, to act as a membrane fusogen by inducing the fusion of the viral envelope membrane with the membrane of the endosome. This expels the viral RNA into the cytoplasm, where it can begin to replicate. 

The precise chemical interactions between an adhesin and its receptor are also important. For example, direct- and water-mediated hydrogen bonds are the most important interactions within the carbohydrate-recognition domain in carbohydrate-binding adhesins on the host cell surface (Weis and Drickamer, 1996). Nonpolar van der Waals interactions and hydrophobic "stacking of the receptor oligosaccharide rings with aromatic amino acid side chains of the bacterial adhesin protein also contribute to oligosaccharide-protein interactions. X-ray structural... 

As described earlier in Section IV.A., several of the carbohydrate sequences that serve as receptors for enteric pathogens have been identified. For EPEC, these receptors are located on the surface of host epithelial cells and are often comprised of galactose, N-acetyl-galactosamine, lactosyl... 

In summary, our approach of using cyclopeptides with natural amino acids and 3-aminobenzoic acid subunits for the development of macrocydic receptors has afforded remarkably efficient hosts. The cation affinity of 4b, for example, exceeds that of many calixarene derivatives. Even more interesting is the high anion affinity of 5 in aqueous solution. By introdudng additional functional groups such as car-boxylates to the periphery of the cavity, we recently also obtained cydopeptides that interact with neutral substrates, for example, carbohydrates [25]. Our peptides therefore represent a versatile dass of artificial receptor that should prove useful in supramolecular and bioorganic chemistry. 

GSLs play crucial roles in functions of the nervous system and skin, cell growth and differentiation, infections, cancer, and immune response [1, 2, 12], Owing to their strategic position in membranes, they interact with toxins, bacteria, and viruses. They form membrane lipid rafts and present the attached carbohydrates as cell-surface receptors and, thus, serve as portals of entry for pathogens through carbohydrate-protein interactions [13]. For example, HIV entry is mediated by GalCer receptors of the host cells [14],... 

FIGURE 16.1 Multivalent binding of a bacterium to the clustered carbohydrate ligand carrying matching terminal carbohydrate residue(s) found in the host cell surface. The multivalent interaction prevents the attachment of the bacterium to the host cell surface. The functional role of the linker is the optimal presentation of the glycan into the binding site of the receptor, but it may also be involved in additional hydrophobic contacts. 

The adhesion protein FimH mediates the attachment of uropathogenic E. coli strains with the host cell glycocalyx and specifically recognizes mannosylated structures. In 2002, Lin et al. first demonstrated that the glyco-AuNP can be used as a probe for staining the binding protein on the cell surface through carbohydrate-receptor interactions [67], Man-AuNPs were used to visualize the FimH adhesins on the type I pili of E. coli via transmission electron microscopy. 

B-cell receptor (membrane-bound immunoglobulin) recognizes native or denatured forms of proteins or carbohydrates in soluble, particulate, or cell-bound form. B cells are particularly important in defending the host against extracellular patho-... 

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