Glycosaminoglycans and Proteoglycans

Introduction of Glycosaminoglycans and Proteoglycans

Glycosaminoglycans (GAGs), also known as mucopolysaccharides, are linear and heterogeneous sulfated glycans composed of repeating disaccharide units. And these repeating units consist of hexosamine units and alternating uronic acid (UA). The UA units can also be divided into β-D-glucuronic acid (GlcA) or α-L-iduronic acid (IdoA), while amino sugars can be based on glucose (Glc) or galactose (Gal). The arrangement of these units in the GAG framework produces a rich GAG family. The length of the GAG chain varies greatly between different GAG types, resulting in a very wide range of molecule weight. The structural variation and heterogeneity of GAGs allow the binding to a variety of extracellular proteins, leading to a variety of biomedical effects.

Fig 1. Structural representations from the crystal structures of some illustrative GAG-protein complexes in PDB.^{1, 2}

Occur in connective tissue, proteoglycans (PGs) are highly glycosylated proteins that consist of a core protein with one or more covalently attached glycosaminoglycan (GAG) chain(s). PGs are an important component of the animal extracellular matrix. Its protein component is always synthesized by ribosomes and then translocated into the rough endoplasmic reticulum. The completed PGs are exported in secretory vesicles to the extracellular matrix of the tissue.

Fig 2. Schematic cartoon images (not to scale) for PGs on the cell surface and in the ECM.^{1, 2}

Pharmaceutical Applications of Glycosaminoglycans and Proteoglycans

• GAG Heparin (HP) has been widely used for the treatment of thromboembolic disorders.
• GAG chondroitin sulfate (CS) has been served as an alternative therapeutic against osteoporosis and osteoarthritis.
• GAG keratan sulfate (KS) is the main functional component of the cornea and can be used as the active ingredient in eye drops.
• GAG hyaluronic acid (HA) is the important component of skin ECM that can be used in cosmetic development.
• PGs can combine with collagen to form cartilage.
• PGs participate in the binding of cations and water to regulate the movement of molecules through the matrix.
• PGs affect the activity and stability of proteins and signal molecules in the matrix.

Associated Diseases of Glycosaminoglycans and Proteoglycans

Mucopolysaccharidosis is a genetic disease characterized by the inability to break down proteoglycans. Mutations in the gene encoding the galactosyltransferase B4GALT7 cause the spine dysplasia form of Ehlers-Danlos syndrome.

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References

1. Pomin, Vitor H., and Barbara Mulloy. "Glycosaminoglycans and proteoglycans." Pharmaceuticals 11.1 (2018): 27.
2. Under Open Access license CC BY 4.0, without modification.

Resources

• N-glycans
• O-glycans
• GPI-anchored Glycoprotein
• Glycosphingolipid