Cell-surface glycoconjugates

Cell-surface glycoconjugates, comprising glycoproteins, glycolipids, and proteoglycans, constitute the glycocalyx, a dense carbohydrate layer essential for cellular identity and environmental interaction (Varki, 2017). These molecules mediate critical biological functions, including cell-cell recognition, adhesion, and the modulation of growth factor signaling (Pinho & Reis, 2015). In pathological states such as cancer, aberrant glycosylation leads to the presentation of tumor-associated carbohydrate antigens (TACAs), which facilitate tumor progression, metastasis, and evasion of the immune system (Munkley & Elliott, 2016). As therapeutic targets, they are exploited through monoclonal antibodies like dinutuximab, which targets the GD2 ganglioside, and various vaccines designed to elicit an immune response against specific glycan motifs (Zhou & Cheng, 2020). Additionally, many pathogens, including the influenza virus and SARS-CoV-2, utilize these surface glycans as receptors for host cell entry, making them focal points for antiviral drug development (Watanabe et al., 2020). However, the high degree of structural diversity and the presence of similar glycans on normal tissues present significant challenges for achieving high therapeutic selectivity.

Other names

GlycocalyxCell-surface carbohydratesMembrane-bound glycansSurface glycoproteinsSurface glycolipidsSurface proteoglycans

Therapeutic agents target cell-surface glycoconjugates by binding to specific glycan epitopes or their associated protein/lipid scaffolds to trigger immune-mediated cell death (e.g., ADCC), block receptor-ligand signaling, or prevent pathogen entry into host cells.