Secondary structures of hyaluronate and chondroitin sulphates. A 1H n.m.r. study of NH signals in dimethyl sulphoxide solution

Scott, J. E.; Heatley, Frank; Moorcroft, D; Olavesen, Anthony H.

doi:10.1042/bj1990829

Cited by 46 publications

(29 citation statements)

References 10 publications

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“…This would be consistent with the DYN models that suggest that the HA chain rapidly interconverts between various helical conformations in solution, some of which make such direct interactions [38]. It is to be noted that the secondary structure models for other glycosaminoglycans [9,39,40], which were derived in the same manner as that of HA, may therefore also be flawed. Nevertheless, differences in temperature coefficients and the slightly retarded rate of solvent exchange between interior and end groups indicate that the adjacent GlcA ring is having some effect on interior amide groups.…”

Section: Discussionmentioning

confidence: 52%

Hyaluronan: the absence of amide–carboxylate hydrogen bonds and the chain conformation in aqueous solution are incompatible with stable secondary and tertiary structure models

Blundell

DeAngelis

Almond

2006

Biochemical Journal

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Contradictory descriptions for the aqueous solution conformation of the glycosaminoglycan hyaluronan (HA) exist in the literature. According to hydrodynamic and simulation data, HA molecules are stiffened by a rapidly interchanging network of transient hydrogen bonds at the local level and do not significantly associate at the global level. In marked contrast, models derived from NMR data suggest that the secondary structure involves persistent hydrogen bonds and that strong associations between chains can occur to form vast stable tertiary structures. These models require an extended 2-fold helical conformation of the HA chain and specific hydrogen bonds between amide and carboxylate groups. To test these descriptions, we have used 15N-labelled oligosaccharides and high-field NMR to measure pertinent properties of the acetamido group. The amide proton chemical shift perturbation and carboxylate group pK(a) value are inconsistent with a highly populated hydrogen bond between the amide and carboxylate groups. Amide proton temperature coefficients and chemical exchange rates confirm this conclusion. Comparison of oligomer properties with polymeric HA indicates that there is no discernible difference in amide proton environment between the centre of octasaccharides and the polymer, inconsistent with the formation of tertiary structures. A [1H-1H-15N] NOESY-HSQC (heteronuclear single-quantum correlation) spectrum recorded on an HA octasaccharide revealed that amide groups in the centre are in a trans orientation and that the average solution conformation is not an extended 2-fold helix. Therefore the two key aspects of the secondary and tertiary structure models are unlikely to be correct. Rather, these new NMR data agree with descriptions from hydrodynamic and simulations data.

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Section: Discussionmentioning

confidence: 52%

Hyaluronan: the absence of amide–carboxylate hydrogen bonds and the chain conformation in aqueous solution are incompatible with stable secondary and tertiary structure models

Blundell

DeAngelis

Almond

2006

Biochemical Journal

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“…C3 is an estimate of the concentration at which a transition from "semi-flexible" to " flexible disordered" chains occur.38 Since hyaluronate, unlike most polyelectrolytes studied, has 5: < 1, Weill's Eq. (10) can be slightly altered to get C3 (mg/mL) = lo00 M,[32z2No( e2/ckbT)3] -' (7) which is about 2.8 mg/mL. Thus, hyaluronate of 0.1-1.2 mg/mL lies in the upper part of this range, and according to Wei11,38 should not be strongly ordered.…”

Section: Discussionmentioning

confidence: 99%

The effects of pH on hyaluronate as observed by light scattering

Reed

1989

Biopolymers

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Hyaluronate was investigated over a wide pH range, and at near zero and intermediate ionic strength, using dynamic and total intensity light scattering. Commercially obtained rooster comb hyaluronate was purified, and solutions were prepared in pure water by low-power bath ultrasonication and subsequent filtering. These solutions were of low polydispersity and appeared to contain single molecules of hyaluronate. Despite the absence of added electrolyte, these solutions yielded well-behaved Zimm plots. Increasing ionic strength and changing pH decreased radii of gyration and increased diffusion constants. Except for what appeared to be slow hydrolysis at either extreme of pH, molecular weights remained constant under all pH and ionic strength conditions. Under all solvent conditions investigated, diffusion coefficients increased with decreasing hyaluronate concentration. Unsonicated, lightly centrifuged solutions without added electrolyte were polydisperse, and their light scattering intensity was dominated by what appeared to be stable hyaluronate aggregates. The results are interpreted in terms of the polyelectrolyte properties of hyaluronate and its tendency to form stable entanglements, especially at low ionic strength. Previous light scattering studies in the literature on hyaluronate have shown widely varying results. The present article briefly reviews this literature and attempts to explain the variation among the previous results, emphasizing the Kuhn statistical segment length as an indicator of whether results are influenced by polydispersity or contaminants causing hyaluronate aggregation.

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“…23,24 Much of the data used to predict the 2-fold helical and tertiary structure models of HA in aqueous solution comes from NMR experiments that were performed nearly 20 years ago (and some of it not even in water). 7,20,25 Since that time, NMR and computational approaches have advanced considerably and now permit a new molecular description for the local solution conformation of HA and the role of intramolecular hydrogen bonds and water molecules to be developed. Here, we use high-field NMR of 15 N isotopically enriched oligosaccharides to provide residue-specific measurements of conformation and dynamics.…”

Section: Introductionmentioning

confidence: 99%

Hyaluronan: The Local Solution Conformation Determined by NMR and Computer Modeling is Close to a Contracted Left-handed 4-Fold Helix

Almond

DeAngelis

Blundell

2006

Journal of Molecular Biology

111

113

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Secondary structures of hyaluronate and chondroitin sulphates. A 1H n.m.r. study of NH signals in dimethyl sulphoxide solution

Cited by 46 publications

References 10 publications

Hyaluronan: the absence of amide–carboxylate hydrogen bonds and the chain conformation in aqueous solution are incompatible with stable secondary and tertiary structure models

Hyaluronan: the absence of amide–carboxylate hydrogen bonds and the chain conformation in aqueous solution are incompatible with stable secondary and tertiary structure models

The effects of pH on hyaluronate as observed by light scattering

Hyaluronan: The Local Solution Conformation Determined by NMR and Computer Modeling is Close to a Contracted Left-handed 4-Fold Helix

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