Glycosylation Changes as Markers for the Diagnosis and Treatment of Human Disease

Chemical Biology of Cell Surface Oligosaccharides

“…In particular, various influenza strains can discriminate between α2,3-and α2,6-linked sialic acids as well as between Neu5Ac and Neu5Gc. Many less publicized viral pathogens [93], including adenovirus, the BK virus [94], coronavirus, cytomegalovirus, hepatitis virus, HIV [95], Newcastle disease virus, papovavirus, polyoma virus, rabies virus, reovirus, rhinovirus, and rotavirus [96], also rely on sialic acid in part or wholly as a binding epitope for cell entry. Sialic acids also occupy the interface between the host and commensal or pathogenic microorganisms and participate in molecular mimicry, provide nutrition, and interpret cell signaling [97].…”

“…Although doubtless valuable for addressing any of the numerous diseases in which carbohydrates are implicated [95], or unraveling the myriad roles of these complex molecules in healthy cells, the use of MOE in glycomics appears particularly promising for the characterization of O-GlcNAc protein modification aberrations associated with metabolic disorder and diabetes [150,151]. In particular, as outlined in Figure 10-8, the azide-derivatized GlcNAc analog Ac 4 GlcNAc can be incorporated into O-GlcNAc-modified proteins via salvage into the hexosamine pathway (see Fig.…”

Glycobiology and Immunology

“…the cytosolic face of the ER where the sugars are linked to the lipid dolichol phosphate and ultimately involves the improbable translocation of the hydrophilic glycan structure across the membrane via a "flippase" [59,60]. The importance of this preparatory process, reviewed in ample detail elsewhere by us [61] and many others [10,[62][63][64][65], is evidenced in a bevy of congenital disorders of glycosylation (CDG) that arise from biosynthetic missteps and that are usually fatal early in childhood (although a few can be overcome with fairly straightforward remedies such as dietary supplementation of rare sugars such as fucose [66]). …”

“…A survey of global HIV gp120 showed that this glycoprotein had a range of N-linked glycosylation site occupancy of between 18 and 33 with a mean of 25 [240]. This variability is thought to be influenced by competing pressures on the virus, similar to those experienced by influenza [61], where the presence of glycans is driven by their indispensable contributions to viral infectivity and protection against neutralizing antibodies [241,242]. On the other hand, excessive glycosylation masks the necessary receptor ligand binding contacts through steric hindrance and the nonspecifically antiadhesive nature of the glycocalyx, thereby supplying selective pressure that limits the upper range of 1.4 CARBOHYDRATE ANTIGENS glycosylation of the viral particle.…”

Dendrimers in Cancer Treatment and Diagnosis

“…1.6.6.2 Towards Therapeutic Exploitation of Glycosylation Abnormalities found in Cancer Aberrant glycosylation, where the patterns of complex carbohydrate glycoforms found on the surfaces of cancer cells are dramatically different from those on healthy cells, is a hallmark of cancer [174][175][176][177][178]. Efforts to exploit these changes therapeutically, however, have long been stymied by the difficulty of controlling these complex and diverse molecules in an artificial synthetic setting.…”