Heparan sulfate and dermatan sulfate (HS/DS)

Heparan sulfate (HS) and dermatan sulfate (DS) are complex, sulfated glycosaminoglycans (GAGs) that serve as essential components of the extracellular matrix and cell surfaces across all animal tissues. HS plays a pivotal role in regulating biological processes such as cell signaling, adhesion, and blood coagulation by acting as a co-receptor for various growth factors, including fibroblast growth factors (FGFs) and vascular endothelial growth factors (VEGFs) (NCBI, 2023). Dermatan sulfate is similarly involved in wound repair, cardiovascular health, and anticoagulation, specifically through its interaction with heparin cofactor II (PubMed, 2021). These molecules are primary therapeutic targets in Mucopolysaccharidoses (MPS), a group of lysosomal storage disorders where genetic deficiencies in enzymes like alpha-L-iduronidase or iduronate-2-sulfatase lead to the pathological accumulation of HS and DS, causing progressive multi-organ damage (NIH, 2022). Treatment strategies for these conditions involve enzyme replacement therapies (ERTs), such as laronidase and idursulfase, which are designed to enzymatically degrade the accumulated GAGs and reduce tissue burden (FDA, 2023). Furthermore, HS and DS are increasingly recognized as critical attachment factors for various pathogens, including SARS-CoV-2 and Herpes Simplex Virus, making them targets for the development of novel antiviral entry inhibitors (Nature Communications, 2020).

Other names

GlycosaminoglycansSulfated glycosaminoglycansChondroitin sulfate BHeparitin sulfateAcid mucopolysaccharides

Enzymatic degradation of accumulated substrates in lysosomal storage diseases; competitive inhibition of protein-GAG interactions to block viral entry or growth factor signaling.