Iduronic acid residues, conformational

Just as the primary structure of heparin and heparan sulfate has a wealth of fine detail, depending on its exact provenance and function, so the exact conformation of a stretch of polysaccharide depends on its exact location in the chain. The key to this conformational flexibility lies in iduronic acid residues, which can adopt either the C4 or the conformation (the glucosamine-derived residues are firmly in the C conformation, as are glucuronic acid residues). Interpretation of vicinal proton proton coupling constants of IdoA residues in terms of an equilibrium between just and conformations suggests the equilibrium changes from 60 40 for internal IdoA residues to 40 60 for terminal residues (Figure 4.84(a)). " ... 

Ferro DR, Provasoli A, Ragazzi M, Casu B, Torri G, Bossennec V, Perly B, Sinay P, Petitou M, Choay J. Conformer populations of L-iduronic acid residues in glycosaminoglycan sequences. Carbohydr Res 1990 195 157-167. 

Data obtained from n.m.r. analysis and from potentiometric titration of variously desulphated and periodate-oxidized heparins have supported the interpretation that non-sulphated cx-L-iduronate residues may adopt two ring conformations. The non-sulphated L-iduronic acid residues in heparin and heparin sulphate have been shown to be resistant to periodate oxidation at pH 3.0, under conditions which will oxidize a large proportion of the D-gluc-uronic acid residues. ... 

D2O solutions of natural and synthetic oligosaccharides representing the biologically important sequences of dermatan sulphate, heparan sulphate, and heparin have been analysed by H-n.m.r. spectroscopy. Particular attention was given to the values of the L-iduronic acid residues which were rationalised by force-field calculations, to allow the determination of the relative proportions of conformers ( 4, C ) present. These... 

Some of the L-iduronic acid residues are sulfated at C-2. These residues adopt the 1C conformation. The nonsulfated L-iduronic acid residues can have either the Cl or the 1C conformation. Dermatan sulfate represents a repeating two-monosaccharide heteropolysaccharide with a-1 3 and P-1 4 heterolinkages. 

The conformation of nonsulfated L-idosyluronic acid residues is a controversial issue, especially on account of a possible role of the 2-O-sulfo substituent in determining the relative orientation of biologically relevant groups. However, the interproton coupling-constants observed for (nonsulfated) methyl a-D-idopyranosiduronic acid131 and dermatan sulfate350 are essentially the same as those of the sulfated L-iduronate resi-... 

The ido configuration is present, isolated in the middle of other monosaccharide residues, in the polycondensed chains called glycosaminoglycans of natural polysaccharides dermatan sulfate, heparan sulfate, and heparin. The derivative in question belonging to the L-series is 2-0-sulfo-L-iduronic acid. It is represented (2.34, R = R = H) in a non-conformational manner with the a-L-idopyrano configuration present in these polysaccharides. The L-ido residue is isolated in the sequence, in the centre of the chains attached to 0-1 and 0-4, respectively (Section 17.3). It is found as a mixture of the l- C4 (2.35) and l- Sq (2.36) conformations. The proportion of the skew form varies from 40 to 60% according to the attached oligosaccharide sequences, R and R (Casu et al. 1986). 

The small deviation of j-, and J45 might reflect a slight distortion of the chair form 04(1) of the iduronic acid unit. Anyway the pre ent data are substantially couistent with the disaccharide repeating residues with glucosamine in Ci(D) conformation and iduronic acid in... 

The conformation of dermatan 4-sulfate, in which C5 of the glucuronic acid has been epimerised, is still unsettled. Fibre X-ray data fitted models in which the a-L-IdoA residue was in the conformation better than those in which it was in the 4 conformation. Models containing skew conformers were not considered and NMR studies have since established that in D2O solutions of dermatan 4-sulfate, the a-L-IdoA residues are in the C4 or So conformations. Molecular dynamics simulations have also supported a Sq conformation for the iduronate in dermatan sulfate. ... 

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