Disease relevance of IDURONIC ACID

• When compared with adenoma HS, the iduronic acid 2-O-sulfate content of the carcinoma-derived material was reduced by 33%, and the overall level of N-sulfation was reduced by 20% [1].
• Iduronic acid-containing glycosaminoglycans on target cells are required for efficient respiratory syncytial virus infection [2].
• These findings indicate that the oversulfated C/DSs with low iduronic acid content are possible marker for the fibrogenesis of liver with cirrhosis [3].
• Six mucopolysaccharidosis fibroblast strains (types I, II, IIIB, IVA, VI and VII) contained 2 to 8 times the normal glucuronic acid levels, and types I and II exhibited 10- to 30-fold normal levels of iduronic acid and 40-fold increases in galactosamine [4].
• Inseparable iduronic acid-containing proteoglycan PG(IdoA) preparations of human skin and post-burn scar tissues: evidence for elevated levels of PG(IdoA)-I in hypertrophic scar by N-terminal sequencing [5].

High impact information on IDURONIC ACID

• These increases in enzyme activity were accompanied by corresponding increases in catabolism of heparan and dermatan sulfates, as shown by (a) a decrease in sulfate:uronic ratios of urinary oligosaccharides, (b) an increase in iduronic acid monosaccharide, and (c) a normalization of Bio-Gel P-2 gel filtration profiles [6].
• Oversulfated disaccharides and nonconsecutive iduronic acid-containing units were the requirements for the E-CS/DS chains to bind PTN and to exhibit the neuritogenic activities [7].
• In conclusion, we have selected an antibody that identifies HS oligosaccharides containing N-acetylated glucosamine and 2-O-sulfated iduronic acid residues [8].
• D4ST-1 transfers sulfate to the C-4 hydroxyl of beta1,4-linked GalNAc that is substituted with an alpha-linked iduronic acid (IdoUA) at the C-3 hydroxyl [9].
• Heparan sulfate oligomers showing a composition close to the dimeric repeats of heparin (glucosamine-NSO(3)(6-OSO(3))-iduronic acid(2-OSO(3))) n = 5 and n > 5, where iduronic acid may alternate with glucuronic acid, exhibit affinity for urokinase plasminogen activator and confer specificity on urokinase/urokinase receptor interaction [10].

Biological context of IDURONIC ACID

• The minimal binding site is found in N-sulfated hexasaccharide domains and contains critical 2-O-sulfated iduronic acid residues [11].
• Endocytosis and subsequent degradation of iduronic acid-rich small dermatan sulfate proteoglycan from fibroblast secretions were studied in human fibroblasts [12].
• These elements, in addition to iduronic acid demonstrated previously (L. K. Hallak, P. L. Collins, W. Knudson, and M. E. Peeples, Virology 271:264-275, 2000), partially define cell surface molecules important for RSV infection of cultured cells [13].
• The presence of C-6 sulphate ester on the non-reducing end 2-sulphaminoglucosamine stimulates sulphamate bond hydrolysis and substrate affinity if the adjacent monosaccharide residue is idose or 2-sulphoidose, but strongly inhibits hydrolysis if the adjacent monosaccharide residue is iduronic acid [14].
• More precisely, we found a decrease in the iduronic acid content, associated with down-regulation of the 4-O-sulphation on the GalNAc residues [15].

Anatomical context of IDURONIC ACID

• Heparan sulphate chains with a high degree of sulphation possessed also a significant number of iduronic acid residues and were isolated exclusively from porcine brain, liver and kidney medulla [16].
• Consistent with the binding being a specific interaction, only iduronic acid-containing glycosaminoglycans inhibit the association of the 35S-labeled proteoglycan with calf brain membranes and facilitate the disassociation [17].

Associations of IDURONIC ACID with other chemical compounds

• Structural analysis of N-syndecan from 6-day-old rat brain indicated that the heparan sulfate chains contain sequences of contiguous, N-sulfated disaccharide units with an unusually high proportion (82%) of 2-O-sulfated iduronic acid residues [18].
• Glycosaminoglycans having a high ratio of iduronic acid to glucuronic acid, as well as ones having lower molecular weight, gave the highest detection sensitivity using this method [19].
• The degree of galactosamine N-acetylation, iduronic acid composition, and total uronic acid/hexosamine ratios of the three dermatan sulfates of human skin, DS18, DS28, and DS35 (M. O. Longas et al. (1987) Carbohydr. Res. 159, 127-136), were determined by Fourier transform, proton nuclear magnetic resonance (FT 1H NMR) spectroscopy [20].
• Glucuronic acid, iduronic acid, and their lactones were separated after hydrolysis in formic acid and sulfuric acid [21].
• DS chains of the tumor-associated versican and decorin contained decreased amounts of iduronic acid [22].

Gene context of IDURONIC ACID

• Experiments with selectively desulfated heparins indicated that 2-O-sulfated iduronic acid units, in particular, are of importance to the interaction with HB-GAM, were implicated to a lesser extent [18].
• Biglycan, but not decorin, from atherosclerotic plaque contained significantly reduced amounts of iduronic acid and disulfated disaccharides DeltaDi-2,4S and DeltaDi-4,6S relative to proteoglycan from normal artery [23].
• The biglycan glycosaminoglycan chains were found to contain a similar ratio of 4-sulphate/6-sulphate, but with approx. 40-45% of the glucuronic acid epimerized to iduronic acid [24].
• Thus, analogous proteoglycans from two different tissues, such as DS-PGI from skin and cartilage, possess a core protein with the same primary structure, yet contain glycosaminoglycan chains which differ greatly in iduronic acid content [25].
• The findings showed that iduronic acid content is reduced by 50% in decorin and biglycan, whereas 4-O-sulfation is increased 2-fold in versican [26].

Analytical, diagnostic and therapeutic context of IDURONIC ACID

• Analyses of oligosaccharide fractions and polysaccharides by electrospray mass spectrometry and high-performance liquid chromatography suggest that the differences between the activities of CS-A and CS-C oligosaccharides can be attributed to differences in sulfate content and sulfation pattern and that iduronic acid is not involved in IE binding [27].
• A large glucuronic acid-rich and a small iduronic acid-rich dermatan sulphate proteoglycan were isolated with the use of isopycnic density-gradient centrifugation, ion-exchange and gel chromatography [28].

References