Chondroitin Sulfate Thiol

Glycosaminoglycan (GAGs) is an active polysaccharide containing a large number of -SO^3- and -COO^- groups, also known as acidic mucopolysaccharides. Depending on the composition of the disaccharide units, GAGs usually include hyaluronic acid, heparin, skin chondroitin, keratan sulfate and chondroitin sulfates (CS). Among them, CS is mainly derived from cartilage and connective tissue of animals, forms a special fucosylated structure in sea cucumbers, and exists in the form of proteoglycan in the matrix of brain cells. According to the difference in structure, CS can be divided into three types: chondroitin linear polysaccharide, fucosylated chondroitin sulfate, and chondroitin sulfate proteoglycan. Since chondroitin carries a large amount of negative charge and is easily combined with K⁺, Na⁺, Ca²⁺, etc., metal salts are a common form of CS commercial products. CS has a wide range of sources and a variety of preparation methods. Although it has been reported that egg membrane can be used as a source of CS, it is currently mainly derived from the cartilage tissue of poultry and livestock. In view of the frequent occurrence of various zoonotic diseases (such as swine flu), the safety of terrestrial animal CS has received increasing attention. Studies have shown that aquatic animals such as fish are better sources of CS than mammals. The yield of CS extracted and prepared by traditional methods such as acid hydrolysis and chemical synthesis is generally low, and the purification operation is relatively complicated. In addition, due to the emergence of environmental pollution, abuse of drugs in aquaculture, and antibiotic residues, the trend of microbial fermentation semi-synthesis has increased. CS produced by fermentation has the advantages of being purer, less allergenic, and smaller in molecular weight than animal sources. CS is widely used in health foods, medical pharmaceuticals, tissue engineering, biomaterials and other fields, and therefore has great market potential.

Figure 1. The natural sulfation patterns of the chondroitin sulfates. (Raúl Benito-Arenas, et al. 2019)

The sugar chain of CS contains repeating β-1,3-linked N-acetylgalactosamine and β-1,4-linked D-glucuronodisaccharide units, which are classified according to the position and degree of sulphide into CSO, CSA, CSC, CSD, CSE five types. In addition to the variability in the position of the sulphate group, different sulphate groups also have significantly different biological activities, such as those CS with 3-O-sulpho-glucuronic acid residues has been shown to have the function of stimulating neurite outgrowth, and the sulfated fucose residues of fucose sulfate chondroitin have multiple activities such as anti-inflammatory and hematopoietic stimulation. In the mammalian central nervous system (CNS), CS is usually covalently bound to a core protein (CP) to form a high molecular compound with two basic structures of sugar chain and protein - chondroitin sulfate proteoglycan (CSPG). The core protein primary structure of CSPG is glycine (Gly)-serine (Ser)-Gly sequence, in which the Ser residue is connected to the tetrasaccharide linking region of CS, i.e. GlcA-GalNAc-GalNAc-xylose (Xyl)-O-Ser, and the sugar chains connected to CP can range from one to hundreds. Chondroitin proteoglycan contains an N-terminal G1 domain and a C-terminal G3 domain. The former can bind to hyaluronic acid and connexin, while the latter can bind to glycolipids. Since CSPG contains more than 95% sugar, it is more similar to polysaccharides than proteins in chemical properties. According to the differences in GAGs chains, CSPG is divided into multifunctional proteoglycan, NG2 transmembrane proteoglycan (also called CSPG4), etc..

As a biopolysaccharide, CS has multivalency, controllable molecular weight and strong designability, and is favoured by polymer science researchers. CS has good adhesion, biocompatibility, biodegradability and cell targeting, making it widely used in the preparation of targeted delivery systems, which aim to embed drugs, cells or genes in composite biomaterials, deliver them in a targeted manner and release them under specific conditions, thereby reducing toxic side effects, prolonging the duration of drug action, improving pharmacodynamic functions or overcoming the immunogenicity of inhibitory tissues to reduce the risk of rejection. CS is also widely used as a biological scaffold in bone, cartilage, cornea, skin and nerve tissue engineering.

Alternate Names:
CS
Chondroitin polysulfate
Chonsurid
CSA
CSB
CSC
Chondroitin sulfuric acid
Cartilage sulfate

References:
1. Raúl Benito-Arenas, et al. Chondroitin Sulfate-Degrading Enzymes as Tools for the Development of New Pharmaceuticals. Catalysts. 2019, 9(4), 322.

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