Chondroitin 6-sulfate, conformational

Dermatan sulfate is found in the skin, arterial walls, and tendon where it is a part of another proteoglycan complex. It is about the same size as chondroitin sulfate and is also able to form helical conformations. 

T Maruyama, T Toida, T Imanari, G Yu, RJ Linhardt. Conformational changes and anticoagulant activity of chondroitin sulfate following its O-sulfonation. Carbohydr Res 306 35-43, 1998. 

Model building in the computer is used to analyze the conformational effects of steric interactions between atoms of the polymer skeleton for x-carrageenan, t-carrageenan, A-carrageenan, agar, chondroltin, chondroitin sulfates, dermatan sulfate, keratan sulfate, hyaluronic acid, and related polysaccharides. Over 99% of the conformations are thus excluded and virtually all of the remainder for each polysaccharide lie close together. Predictions are also made from disaccharide crystal structures and checked against experimental results. 

Answer In solution, the negative charges on chondroitin sulfate repel each other and force the molecule into an extended conformation. The polar molecule also attracts many water molecules (water of hydration), further increasing the molecular volume. In the dehydrated solid, each negative charge is counterbalanced by a counterion, such as Na+, and the molecule collapses into its condensed form. 

Within the sodium hyaluronate molecule, reduced flexibility at the glycoside bond causes a rotation of carbohydrate units along the molecule chain. As a consequence, the molecule shows a flexible, random coil conformation with a certain rigidity. Chondroitin sulfate, however, is a low-molecular-weight glycosaminogly-can and assumes a conformation between the coil described above and a rigid rod. 

Chondroitin sulfate, a 3-1 linked amino sugar, in the presence of methylene blue shows only one unsplit positive Cotton effect at 577 nm. The metachromatic absorption maximum and the ORD crossover conform well at 575 and 573 nm respectively. Here too we can assume that the dye cations are bound in strict geometrical order dictated by the secondary... 

In a short review Pomin has presented the results of structural studies of glycosaminoglycans families including chondroitin sulfate, dermatan, heparin, heparan sulfate, and hyaluronic acid. He has pointed out the pivotal contribution of NMR parameters, particularly scalar and residual dipolar couplings, to the progress in elucidation of the structural, dynamical, conformational and intermolecular binding aspects of the carbohydrates. 

In the wmrk of Meezan and Davidson (1967b) the interesting observation was made that sulfate incorporated into protein-free chondroitin sulfate was located mostly in position 6 of the hexosamine moiety, whereas position 4 w as preferentially sulfated, when the protein portion of the molecule was intact. Although a ready explanation of this finding is currently not available, it may be hypothesized that the protein moiety influences the conformation of the protein polysaccharide in such a fashion as to make the hydroxyl groups in position 4 more accessible to sulfation. 

The following disaccharides and derivatives have been subjected to conformational analysis by n.m.r spectroscopy and/or computational methods cellobiose in aqueous solution, methyl P-xylobioside, methyl P-cellobioside, P-gentibiose, all possible monomethyl ethers of methyl p-lactoside, unsaturated, sulfated disaccharides, such as IS, obtained by cleavage of glycosaminoglycans with lyases, ° chondroitin sulfate-related ctmqmunds, such as 16, the uronic... 

Figure 3. Conformation of the K chondroitin 4-sulfate structure viewed normal to and along the helix axis. The 03 05 hydrogen bonds are shown by broken lines. (Reproduced with permission from ref. 18. Copyright 1983 Academic Press Inc.)...

Attempts to induce conformational changes showed that a second fourfold helix, having a slightly larger repeat (3.72 nm) can be obtained by addition of chondroitin 6-sulfate to the hyaluronate solution. It is not possible to induce a change from the threefold to the fourfold helical form in the condensed state, but the reverse can be achieved, although only by the addition of a calcium salt. A review of the hyaluronic acid conformations was given. 

Molecular modelling suggests that the conformations of chondroitin and its 6-sulfate should be very similar, with that of chondroitin 4-sulfate somewhat different because of the restrictions on j/ imposed by the sulfate group for the p-(1 3) linkage. ... 

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