Glycosaminoglycans dermatan-sulfate

Contamination from other L-iduronic acid-containing glycosaminoglycans (dermatan sulfate and heparan sulfate species) cannot usually be lowered below the 1-2% level, unless repeated precipitations or treatments with resin are made. As will be discussed in Section VIII, extensive... 

Heparin cofactor II, when activated by binding to glycosaminoglycans (dermatan sulfate, heparins, and heparin), inhibits thrombin (24). The 43-kDa serpin, proteinase nexin 1, possesses 30% sequence homology with ATIII and can be activated by binding to heparin to inhibit several serine proteinases including thrombin (25). Proteinase nexin 2 is found within the platelet a-granule and is released when platelets are activated (26). It is able to inhibit factor XIa. 

Aldurazyme (tradename, also known as laronidase) is a recombinant version of one polymorphic variant of the human enzyme a-L-iduronidase. It was approved for general medical use in the USA in 2003 and is indicated for the treatment of patients with certain forms of the rare inherited disease MPS I. MPS I is caused by a deficiency of a lysosomal a-L-iduronidase, which normally catalyses the hydrolysis of terminal a-L-iduronic acid residues from the glycosaminoglycans dermatan sulfate and heparin sulfate. The deficiency results in accumulation of the glycosaminoglycans throughout the body, causing widespread cell and tissue dysfunction. 

Another serine protease inhibitor of the al-antitrypsin family (serpin) is heparin cofactor II (HCII), which also forms a 1 1 complex with thrombin, but does not react with factor Xa [4,10]. The rate of inhibition of thrombin is not only increased by heparinoids but also by the related glycosaminoglycan dermatan sulfate. The identification of an inhibitor variant and site-directed mutagenesis studies on HC II cDNA led to the understanding that the binding sites for heparin and dermatan sulfate may be overlapping but not identical. Further proteinase inhibitors interacting with heparinoids are tissue factor pathway inhibitor and protease nexin-1. 

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 ...

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... 

Pavao, M., Aiello, K., Werneck, C., Silva, L., Valente, A. P., Mulloy, B., Colwell, N. S., Tollefsen, D. M., and Mourao, P. A. (1998). Highly sulfated dermatan sulfates from ascidians. Structure versus anticoagulant activity of these glycosaminoglycans.. Biol. Chem. 273, 27848-27857. 

The glycosaminoglycans of root dentine from permanent human teeth comprise chondroitin-4-sulfate as the major glycosaminoglycan, and chondroitin-6-sulfate, hyaluronic acid, dermatan sulfate, and a non-sulfated galactosaminoglycan in minor quantities309. ... 

Six major classes of glycosaminoglycans There are six major classes of glycosaminoglycans. These include chondroitin 4- and 6-sulfates, keratan sulfate, dermatan sulfate, heparin, heparan sulfate, and hyaluronic acid. 

Heparin cofactor II is a second plasma SERPIN which has resemblance to antithrombin in that it is activatable by glycosaminoglycan binding. This protein has also been called antithrombin BM, dermatan sulfate cofactor, and human leuserpin 2 (88). The existence of this second inhibitor and heparin cofactor was first shown by Briginshaw in 1974 (89). Whereas antithrombin is observed to have progressive antithrombin activity and to also inhibit factor Xa, the second... 

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