Heparan sulfate-binding protein (HSBP)

Heparan sulfate-binding proteins (HSBPs) are a broad and structurally diverse class of proteins that interact with heparan sulfate (HS) glycosaminoglycans found on cell surfaces and within the extracellular matrix [1, 5]. This functional group, often referred to as the heparan sulfate interactome, encompasses hundreds of members, including growth factors (e.g., FGF, VEGF), chemokines, cytokines, and blood coagulation factors such as antithrombin III [2, 10, 15]. HS acts as a critical co-receptor or scaffold, modulating the localization, stability, and signaling potency of these proteins, thereby regulating processes like angiogenesis, inflammation, and tissue repair [6, 7, 10]. In pathological contexts, HSBPs are implicated in tumor progression, chronic inflammatory diseases, and the entry of various pathogens, including SARS-CoV-2 and herpes simplex virus [11, 16, 20]. Therapeutic targeting of HSBPs primarily involves the use of heparin, low molecular weight heparins, or synthetic HS mimetics designed to disrupt or mimic endogenous HS-protein interactions [4, 8, 20]. For example, heparin activates antithrombin III to inhibit coagulation, while HS mimetics like muparfostat are investigated for their ability to sequester pro-angiogenic growth factors in cancer [14, 20]. Despite their therapeutic potential, the promiscuous nature of HS-binding and the structural heterogeneity of the polysaccharide chains present significant challenges for achieving molecular specificity [1, 17]. Notable safety concerns associated with drugs targeting this class include the risk of hemorrhage, heparin-induced thrombocytopenia, and potential off-target effects due to the wide range of proteins affected [14, 19, 21].

Other names

Heparin-binding proteinHSBPHeparan sulfate interactome member

Competitive inhibition of heparan sulfate-protein interactions; allosteric activation of enzyme inhibitors; sequestration of growth factors and cytokines; inhibition of viral attachment and entry