Cell-surface sulfated glycosaminoglycans (GAGs)

Cell-surface sulfated glycosaminoglycans (GAGs) are long, linear, highly anionic polysaccharides composed of repeating disaccharide units, typically found covalently attached to core proteins as proteoglycans [NCBI Bookshelf: Essentials of Glycobiology]. These molecules, including heparan sulfate and chondroitin sulfate, are ubiquitous on cell surfaces and within the extracellular matrix, where their high negative charge density facilitates interactions with a diverse array of protein ligands such as growth factors, chemokines, and morphogens [PubMed: 25631518]. By sequestering these ligands and presenting them to their high-affinity receptors, GAGs act as essential co-receptors that modulate critical signaling pathways involved in cell growth, migration, and tissue repair [UniProt]. In pathological contexts, GAGs are frequently exploited by various pathogens, including SARS-CoV-2 and herpesviruses, as primary attachment factors for host cell entry [Nature Reviews Microbiology]. Furthermore, they play a pivotal role in cancer progression by promoting angiogenesis and facilitating tumor cell invasion through the modulation of the tumor microenvironment [Frontiers in Oncology]. Therapeutic strategies targeting GAGs often utilize sulfated oligosaccharide mimetics to competitively inhibit these interactions, offering potential applications in treating viral infections, inflammatory diseases, and malignancies [DrugBank].

Other names

Heparan sulfateChondroitin sulfateDermatan sulfateKeratan sulfateCell-surface GAGsSulfated polysaccharidesProteoglycan glycan chains

Drugs targeting cell-surface sulfated glycosaminoglycans primarily act as competitive inhibitors or mimetics that disrupt the binding of endogenous ligands, such as growth factors, cytokines, or viral proteins, to the GAG chains [PubMed: 29432139]. For instance, heparin-like molecules can block viral attachment to heparan sulfate co-receptors [Nature Reviews Microbiology]. Additionally, some agents modulate the activity of enzymes like heparanase, which regulates the bioavailability of GAG-bound signaling molecules in the tumor microenvironment [Frontiers in Oncology].