3-O-sulfated heparan sulfate (3-OS HS)

3-O-sulfated heparan sulfate (3-OS HS) is a rare but biologically critical modification of heparan sulfate, a linear polysaccharide found on cell surfaces and in the extracellular matrix [1.1.3, 1.2.3]. This specific sulfation at the 3-OH position of glucosamine residues is catalyzed by a family of 3-O-sulfotransferase (HS3ST) enzymes and creates unique binding motifs for various effector proteins [1.3.1, 1.4.1]. One of its most well-characterized roles is in the anticoagulation cascade, where a specific 3-OS HS pentasaccharide sequence binds and activates antithrombin III to inhibit clotting factors like Factor Xa [1.1.2, 1.4.3]. Beyond its role in blood homeostasis, 3-OS HS serves as a critical entry receptor for Herpes Simplex Virus 1 (HSV-1) by interacting with the viral envelope glycoprotein D [1.3.2, 1.3.4]. Recent studies have also linked 3-OS HS to neurodegenerative conditions, particularly Alzheimer's disease, where it facilitates the cellular uptake and spread of tau protein [1.2.1, 1.2.4]. Consequently, 3-OS HS is a key therapeutic target, with drugs like fondaparinux mimicking its structure for anticoagulation and ongoing research exploring its inhibition to treat viral infections and dementia [1.4.2, 1.4.3].

Other names

3-O-sulfated HS3-O-S HS3-OST-modified heparan sulfateAnticoagulant heparan sulfate3-O-sulfated glucosamine-containing heparan sulfate

3-O-sulfated heparan sulfate acts as a critical binding site for antithrombin III, inducing a conformational change that accelerates the inhibition of Factor Xa and thrombin [1.1.2, 1.4.3]. In viral pathogenesis, it serves as a specific receptor for the Herpes Simplex Virus 1 (HSV-1) glycoprotein D, facilitating viral-host membrane fusion and entry [1.3.1, 1.3.2]. Additionally, it interacts with tau protein and ApoE in the brain, promoting the cellular uptake and aggregation of tau in neurodegenerative pathways [1.2.1, 1.2.2].