N-linked sialic acid-containing glycoconjugates

N-linked sialic acid-containing glycoconjugates are a diverse class of cell-surface and secreted molecules where sialic acid residues are terminally attached to N-linked carbohydrate chains of proteins. These glycoconjugates play a critical role in biological recognition processes, serving as ligands for various receptors such as Siglecs (Sialic acid-binding immunoglobulin-type lectins) and as primary attachment points for numerous pathogens, including influenza viruses and certain coronaviruses (Varki, 2008; Matrosovich et al., 2004). In healthy physiology, they contribute to protein stability, cell-cell adhesion, and the regulation of the immune response by providing "self" signals to the innate immune system (Varki & Gagneux, 2012). In pathological states, such as cancer, altered sialylation patterns (hypersialylation) are frequently observed, promoting tumor metastasis and immune evasion by interacting with inhibitory Siglecs on immune cells (Schauer, 2009). Therapeutic strategies targeting these glycoconjugates often involve neuraminidase inhibitors that prevent viral release or sialidases like DAS181 that enzymatically remove sialic acids to block pathogen entry.

Other names

Sialylated N-glycansSialyl-N-glycoproteinsNeu5Ac-containing N-glycansSialylated N-linked glycoproteinsSialyl-glycoproteins

Drugs targeting these glycoconjugates primarily work by either inhibiting the viral neuraminidase enzyme to prevent the cleavage of terminal sialic acids, thereby trapping viral progeny on the host cell surface, or by using recombinant sialidases (e.g., DAS181) to enzymatically remove the sialic acid receptors from the respiratory epithelium to prevent viral attachment and entry (Varki, 2008; Matrosovich et al., 2004).