Heparan sulfate proteoglycans and sialylated glycoproteins (HSPGs and Sialylated Glycoproteins)

Heparan sulfate proteoglycans (HSPGs) and sialylated glycoproteins are two major classes of negatively charged glycoconjugates that form the glycocalyx on the surface of mammalian cells [NIH, 2022]. HSPGs, such as syndecans and glypicans, consist of a core protein with attached heparan sulfate glycosaminoglycan chains that serve as co-receptors for various growth factors and cytokines, regulating pathways like FGF and VEGF [ResearchGate, 2008]. Sialylated glycoproteins are proteins modified with glycans terminating in sialic acid residues, which contribute to the cell's negative surface charge and are essential for cell-cell recognition and adhesion [MDPI, 2021]. Together, these molecules are critical for maintaining tissue integrity and mediating cellular communication with the extracellular environment [TandfOnline, 2004]. In disease, these molecules are frequently exploited as attachment factors by pathogens, including SARS-CoV-2, influenza, and herpes simplex virus, to facilitate viral entry [NIH, 2022; PLOS, 2018]. In oncology, their overexpression promotes tumor metastasis, angiogenesis, and the uptake of pro-tumorigenic exosomes [PNAS, 2013; ResearchGate, 2008]. Therapeutic strategies include heparan sulfate mimetics like pixatimod and sialidase enzymes like DAS181, which aim to block or remove these glycans to prevent pathological interactions [ACS, 2024; ResearchGate, 2008]. However, targeting these ubiquitous structures poses significant challenges, such as the risk of coagulopathy and the potential to disrupt normal physiological signaling [ResearchGate, 2008; MDPI, 2021].

Other names

Cell surface glycoconjugatesGlycocalyx componentsAnionic cell surface glycansHeparan sulfate proteoglycans and sialic acid-containing glycoproteins

Drugs targeting these molecules primarily act as competitive inhibitors (mimetics) that bind to ligands like viral proteins or growth factors, or as enzymes that modify the cell surface glycans to prevent pathological interactions [NIH, 2022; ResearchGate, 2008].