![]() ![]() It was found that human respiratory viruses uniquely bind 9- O-acetylated α2,8-linked disialoside found on glycosphingolipids 21.ĭespite advances, the roles of distinct O-acetylated sialosides in health and disease remain difficult to explore. Recent analysis of receptor specificities of these viruses infecting different species of animals and humans demonstrated host-specific patterns of receptor recognition in relationship to both the pattern of acetylation and glycosidic linkage type. O-acetylated sialic acids serve also as receptors for many viruses including embecoviruses (family Coronaviridae), toroviruses (Tobaniviridae), and influenza C and D viruses (Orthomyxoviridae) 21. In addition, it can block the activity of bacterial sialidases and by this means protect the integrity of the epithelial mucus barrier. It also substantially reduces the rate of hydrolysis by several human endogenous sialidases thereby regulating properties of glycoconjugates such as turnover and degradation 20. O-acetylation can preclude recognition by glycan binding proteins such as the Siglec immune-receptors and complement protein factor H and as a result can function as a molecular switch 19. Furthermore, there are marked differences in the expression of sialoglycans in different species, which likely is due to evolutionary pressure evoked by host–pathogen interactions 14.Ī growing body of literature associates sialic acid O-acetylation with various diseases including cancer, immune disorders, and infection 15, 16, 17, 18. The expression of sialic acids is regulated in a developmental and tissue-specific manner. The resulting glycotopes can be presented at different underlying glycan moieties and can be part of Asn- and Ser/Thr-linked glycans ( N- and O-linked glycans, respectively), glycolipids as well as free floating glycans such as human milk oligosaccharides. ![]() Further structural diversity comes from different Neu5Ac and Neu5Gc glycosidic linkage types and the most common ones are α2,3-linked to galactose (Gal), α2,6-linked to Gal and N-acetyl-galactosamine (GalNAc) and α2,8-linked to another sialic acid. They can be modified by acetyl esters at the 4-, 7-, 8-, and/or 9-position to give as many as 15 different patterns of O-acetylation 13. N-Acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc) are major forms of sialic acid expressed by mammals. Sialylation of glycans also modulates half-life, immunogenicity, and properties of biologicals 10, 11, 12. Sialoglycans regulate many biological and disease processes 6, 7, 8, and can function as receptor for many pathogens including viruses, bacteria and protozoa 9. ![]() Several pathogenic microorganisms also express sialylated glycoconjugates which are used for molecular mimicry to evade host immune detection 3, 4, 5. Sialic acids are negatively charged nine-carbon monosaccharides that are often part of complex glycans of higher animals 1, 2. It uncovered contrasting sialic acid linkage types of acetylated and non-acetylated sialic acids and provided a rationale for sialic acid binding preferences of equine H7 influenza A viruses. The CCS values were used to characterize O-acetylated sialosides from mucins and N-linked glycans from biologicals as well as equine tracheal and nasal tissues. It is based on the use of a library of synthetic O-acetylated sialosides to establish intrinsic collision cross section (CCS) values of diagnostic fragment ions. Here, we describe a drift tube ion mobility-mass spectrometry approach that can elucidate exact O-acetylation patterns as well as glycosidic linkage types of sialosides isolated from complex biological samples. A lack of analytical methods that can determine exact structures of sialic acid variants is a hurdle to determine roles of distinct O-acetylated sialosides. O-acetylation is a common modification of sialic acids that has been implicated in a multitude of biological and disease processes. ![]()
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