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Periodate oxidation and the shapes of glycosaminoglycuronans in solution.

ABSTRACT: 1. It is proposed that periodate oxidation of glycol groups in the repeating units of polysaccharide molecules can be used to probe differences in polymer shapes in solution. 2. Measurement of second-order rate constants (k2) of periodate-glycol reactions may be compared between polymers and relevant monomers, to assess perturbations due to polymer configuration. 3. Factors effecting the measurement and interpretation of k2 are discussed. Over-oxidation, free-radical side reactions, end-group effects, Donnan equilibria and polymer (or molecular-weight) effects are relevant, but their importance is either small or can be minimized in practice. 4. A small group of glycosaminoglycuronans (chondroitin 4- and 6-sulphates and hyaluronate) are oxidized 50--100 times more slowly than three other glycosaminoglycuronans of similar composition, relevant monomers or three homopolyuronides. 5. A stable configuration in solution is postulated for the periodate-resistant polymers, involving carboxylate, acetamido and hydroxy groups in hydrogen-bonded sequences on alternate sides of the molecule. The more easily oxidizable polyuronides are unable to form this configuration. 6. The effect of temperature on the postulated configuration is investigated through the Arrhenius plot of k2, measured to hyaluronate, chondroitin 6-sulphate and methyl 4-O-methyl-alpha-D-glucopyranoside. Probable transitions at high (around 90 degrees C) temperatures were observed for both polymers, with an additional transition at about 37 degrees C in the case of hyaluronate. 7. L-Iduronic acid can take up different conformations depending on the polymer environment.

SUBMITTER: Scott JE

PROVIDER: S-EPMC1185754 | biostudies-other | 1978 Jul

REPOSITORIES: biostudies-other

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Project description:There is a growing interest on glycol-split low-molecular weight heparins (gs-LMWHs), obtained by periodate oxidation of LMWHs, optionally followed by borohydride reduction, as potential anticancer and anti-inflammatory drugs. However, their structural characterization is still a challenging task, mainly because of the high microheterogeneity of the starting material. In addition, susceptibility to oxidation of some end-groups of LMWHs induces additional heterogeneity, making analysis of gs-LMWHs more complex. In our previous study we showed that 1,6-anhydro-d-mannosamine N-sulfate was affected by periodate, while its epimer 1,6-anhydro-d-glucosamine N-sulfate was resistant. In order to understand the apparently anomalous behavior of terminal 1,6-anhydro-d-mannosamine N-sulfate residues, in the present work we have studied by NMR spectroscopy and LC/MS the behavior of the reducing end amino sugar residues of the tetrasaccharides, isolated from the LMWH enoxaparin, in the presence of periodate. Their molecular mechanics conformational characterization has been also performed. We have shown that the C(2)-C(3) bond of the 1,6-anhydro-d-mannosamine residue can be split by periodate despite the N-substitution. Moreover, we have found that both terminal d-mannosamine N-sulfate and d-glucosamine N-sulfate, lacking the 1,6-anhydro-bridge, can be also oxidized by periodate but with a significantly lower rate. The present results suggest that the cis-e-/a-position of OH and NHSO3(-) groups of N-sulfated 1,6-anhydro-d-mannosamine is not the only factor that makes these end residues susceptible to the oxidation. The 1,6-anhydro-bridge that 'blocks' the ring conformation appears another crucial factor for oxidation to occur. Moreover, we have shown that controlling the reaction time could permit to selectively split non-sulfated iduronic acids of enoxaparin chains without oxidizing terminal amino sugar residues, a finding that may be useful to obtain more structurally homogeneous gs-LMHWs.

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Periodate oxidation and the shapes of glycosaminoglycuronans in solution.

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