Chondroitin glycosaminoglycan

Another example in which the reaction of a glycosylthiol 52 displaces a triflate on a second sugar 53, generating a thiodisaccharide 54 is reported in Fig. 24 for the synthesis of a mimetic of glycosaminoglycan chondroitin (55).53... 

Sulfation of the carbohydrate chain occurs after the monosaccharide to be sulfated has been incorporated into the growing carbohydrate j chain. The source of the sulfate is 3 -phosphoadenosyl-5 -phospho-sulfate (PAPS, a molecule of AMP with a sulfate group attached to the 5-phosphate). Sulfotransferases cause the sulfation of the carbohydrate chain at specific sites. [Note An example of the synthesis of a sulfated glycosaminoglycan, chondroitin sulfate, is shown in Figure 14.11.] PAPS is also the sulfur donor in glycosphingolipid synthesis. [Note A defect in the sulfation process results in one of several autosomal recessive disorders that affect the proper development and maintenance of the skeletal system. This illustrates Ihe importance of the sulfation step.]... 

Fig. 5-21 Schematic representation of the linkage between the glycosaminoglycan chondroitin sulfate and a serine residue of the core protein.

Increase in chondroitin sulfate-4 chondroitin sulfate-6 ratio Increase in proteases, especially neutral metalloproteinases Decrease in glycosaminoglycans—chondroitin sulfate and keratan sulfate... 

An enzyme that hydrolyses dermatan sulphate, but neither chondroitin 4-sulphate nor chondroitin 6-sulphate, has been isolated from Flavobacterium heparinum grown in the presence of glycosaminoglycans. Chondroitin and dermatan sulphates and disaccharides obtained from them induced the synthesis of this enzyme, which was separated from a chondroitin sulphate lyase AC. The enzyme acted on dermatan sulphate to give an unsaturated, sulphated disaccharide and higher oligosaccharides. 

Denuziere, A., Ferrier, D. and Domard, A. (2000) Interactions between chitosan and glycosaminoglycans (chondroitin sulfate and hyaluronic acid) physicochemical and biological studies, Ann. Pharmaceut. Francoises 58,47-53. 

Danaparoid (Orgaran mean MW, 6,000 Da) is a mixture of nonheparin glycosaminoglycans derived from pig gut (dermatan sulfate, heparan sulfate, chondroitin sulfate). Die anti-Xa/anti-IIa ratio (22 1) is even greater than seen with LMWH. Die anti-IIa effect may be mediated in part by dermatan sulfate, which catalyzes thrombin inhibition by heparin cofactor II. 

Fig. 34.—Circular Dichroism of Glycosaminoglycans (a) Hyaluronic Acid (b) Heparan Sulfate from Normal Mammalian Tissue (c) Chondroitin 4-Sulfate (d) Dermatan Sulfate ...

Fig. 19 Structures of glycosaminoglycans (A) chondroitin-4-sulfate (B) heparin sulfate (C) dermatin sulfate (D) hyaluronic acid (E) chondroitin-6-sulfate (F) keratin sulfate. 

Dermatan sulfate, also termed chondroitin sulfate B, a related glycosaminoglycan constituent of connective tissue, was known to be composed of galactosamine and a uronic acid, originally believed to be glucuronic acid but then claimed to be iduronic acid based largely on color reactions and paper chromatography. However, the d or L-enantiomer status of the latter monosaccharide was not clear. Jeanloz and Stoffyn unequivocally characterized the monosaccharide as L-iduronic acid by consecutive desulfation, reduction, and hydrolysis of the polysaccharide, followed by isolation of the crystalline 2,3,4-tri-0-acetyl-l,6-anhydro-/ -L-idopyranose, which was shown to be identical to an authentic specimen synthesized from 1,2-0-isopropylidene-/ -L-idofuranose.34... 

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