Disease relevance of (2R,3S,4S,5R,6R)-6-[(2R,3R,4R,5R,6R)-3-acetamido-2-hydroxy-6-methylol-5-sulfoxy-tetrahydropyran-4-yl]oxy-3,4,5-trihydroxy-tetrahydropyran-2-carboxylic acid

• Chondroitinase B from Flavobacterium heparinum is the only known lyase that cleaves the glycosaminoglycan, dermatan sulfate (DS), as its sole substrate [1].
• This suggests that changes in arterial glycosaminoglycans (especially the ratio of heparan sulphate to dermatan sulphate) precede the development of lesions in diabetes and may be important in atherogenesis [2].
• We report here that extracellular proteinases secreted by the human pathogens Pseudomonas aeruginosa, Enterococcus faecalis and Streptococcus pyogenes release dermatan sulphate by degrading dermatan sulphate-containing proteoglycans, such as decorin [3].
• The walking performance of peripheral arterial obstructive disease patients was used to evaluate the usefulness of sulodexide, a glycosaminoglycan containing fast moving heparin and dermatan sulphate [4].
• Changes in the structure and metabolism of fibrillin, a microfibril associated protein, can result in classical Marfan syndrome, and reduced expression of decorin, a small extracellular chondroitin sulphate/dermatan sulphate proteoglycan, has been observed in fibroblasts of a patient with neonatally lethal Marfan syndrome [5].

Psychiatry related information on (2R,3S,4S,5R,6R)-6-[(2R,3R,4R,5R,6R)-3-acetamido-2-hydroxy-6-methylol-5-sulfoxy-tetrahydropyran-4-yl]oxy-3,4,5-trihydroxy-tetrahydropyran-2-carboxylic acid

• This impression is based on the finding that the glycosaminoglycan, heparan sulphate, is found associated with neurofibrillary tangles, neuritic plaques and neuropil threads while dermatan sulphate, chondroitin sulphate and keratan sulphate immunoreactivity is found around neuritic plaques in brains of Alzheimer's disease patients [6].

High impact information on (2R,3S,4S,5R,6R)-6-[(2R,3R,4R,5R,6R)-3-acetamido-2-hydroxy-6-methylol-5-sulfoxy-tetrahydropyran-4-yl]oxy-3,4,5-trihydroxy-tetrahydropyran-2-carboxylic acid

• ELISA studies and crossed immunoelectrophoresis demonstrated that purified dermatan sulphate proteoglycans isolated from bovine sclera did not react with these antibodies but that the antibody to cartilage proteoglycan reacted with other molecules extracted from sclera [7].
• Analysis of the protein profile bound to immobilized dermatan sulphate showed that on a molar basis, histidine-rich glycoprotein and apolipoprotein E were the most abundant proteins specifically bound, together with significant amounts of fibrinogen and vitronectin [8].
• Dermatan sulphate induces plasminogen activator release in the perfused rat hindquarters [9].
• On laminin surfaces, DS and HS had no effect on neurite growth from both cerebellar and DRG neurons [10].
• Decorin, a small dermatan-sulfate proteoglycan, participates in extracellular matrix assembly and influences directly and indirectly cell behavior via interactions with signaling membrane receptors and transforming growth factor (TGF)-beta [11].

Chemical compound and disease context of (2R,3S,4S,5R,6R)-6-[(2R,3R,4R,5R,6R)-3-acetamido-2-hydroxy-6-methylol-5-sulfoxy-tetrahydropyran-4-yl]oxy-3,4,5-trihydroxy-tetrahydropyran-2-carboxylic acid

• The glioma cells produced little dermatan sulphate and the dermatan sulphate chains differed from those of normal cultures with respect to the distribution of iduronic acid residues [12].
• Biosynthesis of dermatan sulphate. Defructosylated Escherichia coli K4 capsular polysaccharide as a substrate for the D-glucuronyl C-5 epimerase, and an indication of a two-base reaction mechanism [13].

Biological context of (2R,3S,4S,5R,6R)-6-[(2R,3R,4R,5R,6R)-3-acetamido-2-hydroxy-6-methylol-5-sulfoxy-tetrahydropyran-4-yl]oxy-3,4,5-trihydroxy-tetrahydropyran-2-carboxylic acid

• Therefore, only a limited picture of the functional role of active site residues in DS depolymerization was presented in previous structural studies [1].
• In addition, the Arg-364 mutant had an altered product profile after exhaustive digestion of DS, suggesting a role for this residue in defining the substrate specificity of chondroitinase B [1].
• Exogenous heparan/dermatan sulphate chains behave similarly as either potentiators or inhibitors of cell motility (depending upon the assay) [14].
• During infection, proteoglycan degradation and release of dermatan sulphate may therefore represent a previously unknown virulence mechanism, which could serve as a target for novel antibacterial strategies [3].
• The pharmacokinetics of MF 701 infusion are consistent with those previously described after i.v. bolus administration [15].

Anatomical context of (2R,3S,4S,5R,6R)-6-[(2R,3R,4R,5R,6R)-3-acetamido-2-hydroxy-6-methylol-5-sulfoxy-tetrahydropyran-4-yl]oxy-3,4,5-trihydroxy-tetrahydropyran-2-carboxylic acid

• In addition, transformed chondroblasts initiated the synthesis of HS and increased their synthesis of DS to levels that matched those of transformed fibroblasts [16].
• In contrast, control chondroblasts synthesized very low levels of HA and DS, no HS, and very high levels of CS [16].
• Biglycan and decorin are small chondroitin/dermatan sulphate proteoglycans in the extracellular matrix of connective tissue that belong to the family of structurally related proteoglycans called small leucine-rich repeat proteins [17].
• These mutations lead to a deficiency of the glycosidase alpha-L-iduronidase (IDUA), which is required for the degradation of heparan sulphate and dermatan sulphate and thus the storage of these glycosaminoglycans in the lysosome [18].
• Interestingly, although cell responsiveness to hepatocyte growth factor is not restored by exogenous heparan/dermatan sulphate chains, it is by an immobilised heparan sulphate proteoglycan substratum [14].

Associations of (2R,3S,4S,5R,6R)-6-[(2R,3R,4R,5R,6R)-3-acetamido-2-hydroxy-6-methylol-5-sulfoxy-tetrahydropyran-4-yl]oxy-3,4,5-trihydroxy-tetrahydropyran-2-carboxylic acid with other chemical compounds

• Control fibroblasts synthesized low levels of hyaluronic acid (HA), and dermatan sulfate (DS), moderate levels of heparan sulfate (HS), and high levels of chondroitin sulfate (CS) [16].
• The rate of bleeding complications in all operated patients was 6.9% with dermatan sulphate and 7.5% with heparin (confidence interval for the absolute risk difference, -4.1 to 2.9%) [19].
• Specific association of iduronic acid-rich dermatan sulphate with the extracellular matrix of human skin fibroblasts cultured on collagen gels [20].
• Desmin 370, a low molecular weight dermatan sulfate, reduces the weight of preformed thrombi in rats made afibrinogenemic by ancrod [21].
• The cynomolgus monkey trabecular GAGs include: 12.8% HA, 14.3% CS, 15.2% DS, 42.1% KS, and 15.6% HS [22].

Gene context of (2R,3S,4S,5R,6R)-6-[(2R,3R,4R,5R,6R)-3-acetamido-2-hydroxy-6-methylol-5-sulfoxy-tetrahydropyran-4-yl]oxy-3,4,5-trihydroxy-tetrahydropyran-2-carboxylic acid

• Sequence analysis of the N-terminal 20 amino acid residues reveals the presence of a single site for the potential substitution of dermatan sulphate at residue 4 of DS-PGII and two such sites at residues 5 and 10 for DS-PGI [23].
• Furthermore, the dermatan sulphate chains synthesized on the xyloside in TGF-beta-treated fibroblasts contained a larger proportion of D-glucuronosyl residues than those of the control [24].
• All these effects can be strongly inhibited by the addition of an antibody to CD44, except CS6 and DS [25].
• The disease is caused by the inability to degrade dermatan sulphate and heparan sulphate due to mutations in the iduronate-2-sulphatase gene (IDS) [26].
• Additional experiments demonstrated that dermatan sulphate and disaccharides of the structure [DeltaUA(2S)-GalNAc(4,6S)], or sucroseoctasulphate, inhibited the degradation of LL-37 [27].

Analytical, diagnostic and therapeutic context of (2R,3S,4S,5R,6R)-6-[(2R,3R,4R,5R,6R)-3-acetamido-2-hydroxy-6-methylol-5-sulfoxy-tetrahydropyran-4-yl]oxy-3,4,5-trihydroxy-tetrahydropyran-2-carboxylic acid

• Dermatan sulphate proteoglycan is lost from the tissue and is present at increased concentrations in the organ culture supernatants, indicating that T cell activation has led to solubilisation of lamina propria proteoglycans [28].
• Potential interactions between dermatan sulphate chains were studied by gel filtration [29].
• Dermatan sulphate proteoglycans from sclera examined by rotary shadowing and electron microscopy [30].
• A method for the sequence analysis of dermatan sulphate [31].
• An iodinated derivative of dermatan sulphate was administered by the intravenous, subcutaneous and oral routes to healthy human volunteers in conjunction with unlabelled dermatan sulphate [32].

References