Cell-surface glycoprotein carbohydrate (Glycan)

Cell-surface glycoprotein carbohydrates, often referred to as glycans, are complex sugar chains covalently attached to proteins on the plasma membrane, forming a dense layer known as the glycocalyx. These molecules serve as critical mediators of biological processes, including cell-cell recognition, adhesion, and the modulation of immune signaling pathways (1.1.1, 1.1.3). In healthy physiology, they are essential for maintaining tissue integrity and facilitating the proper folding and stability of membrane proteins (1.1.2, 1.4.1). However, aberrant glycosylation is a well-recognized hallmark of various diseases, particularly cancer, where altered glycan structures like Sialyl-Lewis X and the Tn antigen promote tumor metastasis, invasion, and immune evasion (1.2.5, 1.4.2). Therapeutically, these carbohydrates are targeted to disrupt pathological interactions or to deliver payloads specifically to diseased cells. For instance, monoclonal antibodies like dinutuximab target specific glycans to trigger immune-mediated destruction of neuroblastoma cells, while glycomimetics such as uproleselan are designed to block selectin-mediated adhesion in inflammatory and hematologic conditions (1.2.1, 1.2.3). Additionally, the high specificity of certain glycan-receptor interactions, such as the binding of N-acetylgalactosamine (GalNAc) to the asialoglycoprotein receptor in the liver, is widely exploited for the targeted delivery of RNA-based therapeutics (1.2.4). Despite their potential, the structural complexity and widespread distribution of glycans present significant challenges for achieving high therapeutic selectivity and minimizing off-target effects (1.4.2, 1.5.1).

Other names

Cell surface glycanOligosaccharideGlycoconjugateTumor-associated carbohydrate antigen (TACA)GlycocalyxSurface carbohydrate

Drugs targeting these molecules typically act by inhibiting cell-cell adhesion (e.g., selectin antagonists), inducing antibody-dependent cellular cytotoxicity (ADCC) against tumor cells, blocking viral or bacterial attachment to host cells, or utilizing specific glycan-receptor interactions for targeted drug delivery (e.g., GalNAc-conjugates).