A water molecule participates in the secondary structure of hyaluronan

Heatley, Frank; Scott, J. E.

doi:10.1042/bj2540489

Cited by 129 publications

(105 citation statements)

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“…In H20-containing solution, a water bridge substituted for the direct H bond N H + O -e . r 0 [12]. Computer simulation using molecular dynamics confirmed that the experimentally observed twofold helix was preferred and stable in water, but in vucuo, threefold and fourfold configurations were also adopted, within the same chain [13].…”

mentioning

confidence: 71%

Secondary and tertiary structures involving chondroitin and chondroitin sulphates in solution, investigated by rotary shadowing/electron microscopy and computer simulation

Scott

Chen

Brass

1992

European Journal of Biochemistry

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Rotary shadowing/electron microscopy of chondroitin 6-sulphate (CS6) and 4-sulphate (CS4) showed that the former, but not the latter, aggregated to mesh works. Preparations made from salt (ammonium acetate) solutions showed enhanced aggregation. Computer modelling, using molecular mechanics and dynamics, was applied to secondary structures (twofold helices) derived from NMR studies, to determine geometric and energetic constraints on duplex and higher-aggregate formation. The calculations suggested that chondroitin, CS6 and undersulphated CS4 could form duplexes, while CS4 could not, thus bridging the gap between atomic dimensions (NMR) and high polymer scale (clcctron microscopy). Calculations suggested that water structure helped to stabilise the twofold helix. It is proposed that the twofold helical, flat, tape-like molecules aggregate via hydrophobic bonding between the very extensive hydrophobic patches (9 CH units) repeated on alternating sides of the polymers. The negative charge of the polyanions opposes aggregate formation. Calculations showed that duplexes were formed with decreasing stability as the charge density increased, and as the charge was concentrated towards the centre line of the polymer (i.e. in CS4). The unsulphated polymer chondroitin could form duplexes and higher aggregates as readily as hyaluronan. Hyaluronan was calculated to form stable heteroduplexes with CS6 and CS4. The frequency and positioning of the sulphate-ester group within the polymer thus determines whether the molecule participates in duplex formation.The extra-cellular matrix of mammalian connective tissues is based on two structural elements: (a) insoluble fibres, predominantly collagenous ; (b) soluble polyanions, of a largely carbohydrate nature. The former resist or transmit tensile stresses, whereas the latter resist and absorb compressive Forces [I]. The two elements interact with each other in a very specific manner [2], implying that there are complementary binding sites, with the corollary that the shapes of the interactants must be at least semipermanent. The tertiary structures of collagen molecules, and to some extent the quaternary structure of collagen fibrils, are established [3], but the soluble polyanions have not been investigated as extensively, partly because they function in aqueous solution. There was doubt that they had stable secondary structures, or formed tertiary structures based on glycan/glycan interactions.The soluble carbohydrate polyanions are of two types, the proteoglycans, consisting of a polypeptide core with long polyanionic glycosaminoglycan (GAG) side chains, and hyaluronan (HA), a GAG that is not covalently attached to protein. [2], corresponded to characteristic differences in appearance in electron microscopy, after rotary shadowing [4-61. HA and the proteoglycan GAG chondroitin sulphate (CS), keratan sulphatc and dermatan sulphate consist of repeating disaccharide units, comprising glucosamine or galactosamine, and a uronic acid (glucuronic or iduronic) except in the case of k...

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confidence: 71%

Secondary and tertiary structures involving chondroitin and chondroitin sulphates in solution, investigated by rotary shadowing/electron microscopy and computer simulation

Scott

Chen

Brass

1992

European Journal of Biochemistry

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“…The properties of these forms depend on the concentration and molecular weight of HA in the aqueous solution. Heatley et al (23) suggested that a high concentration of higher molecular weight HA (Ͼ1.0 mg/mL) produces random coils or chains that become entangled to form extended three-dimensional structures, and chain-chain overlap occurs. When the HA concentration is Ͻ0.1%, the HA molecules do not overlap (24).…”

Section: Discussionmentioning

confidence: 99%

Hyaluronan Reduces Surfactant Inhibition and Improves Rat Lung Function after Meconium Injury

Goerke

Clements

et al. 2005

Pediatr Res

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Hyaluronan (HA), an ionic polymer, is normally present in the alveolar subphase and is known to decrease lung surfactant inactivation caused by serum in vitro. In this study, we examined whether HA can ameliorate the inactivating effects of meconium in vitro and in vivo. Surface activities of various mixtures of Survanta, HA, and meconium were measured using a modified pulsating bubble surfactometer. With meconium, almost all surface activity measures were improved by the addition of HA of several molecular weights at a concentration of 0.25%. Anesthetized, paralyzed rats were maintained on positive-pressure ventilation. After lung injury by instillation of meconium, they were treated with Survanta, Survanta with HA, or control mixtures. Serial measures of blood gases and peak inspiratory pressure were recorded for the duration of the experiment. When the Survanta plus HA group was compared with the Survanta alone group, arterial oxygen tension averaged 117% higher, peak inspiratory pressure was 27% lower at the end of the experiment, and lung compliance also showed significant improvement. These results indicate that HA added to Survanta decreases inactivation caused by meconium in vitro and improves gas exchange and pulmonary mechanics of animals with meconiuminduced acute lung injury. Abbreviations HA, hyaluronan (hyaluronic acid) PEG, polyethylene glycol PIP, peak inspiratory pressure PV, pressure-volume SA, surface area ⌬A 10 , percentage decrease in surface area from the maximum to reach a surface tension of 10 mN/m Hyaluronan (HA) is an ionic polymer of alternating Nacetylglucosamine and glucuronate units. It is one of the glycosaminoglycans that includes chondroitin, keratan, and heparan sulfates. Although HA has a simple chemical structure, it can assume a large number of conformations in aqueous solutions. These conformations allow HA to play many roles in biologic systems, such as being a space filler in the vitreous humor and serving as a viscoelastic substance in joints. In addition, HA interacts with cell surface receptors such as the receptor to HA-mediated motality RHAMM and CD44 (1-3). The biocompatibility of HA has led to many applications, including viscosurgery to allow the creation of space between tissues (4) and lubrication of arthritic joints.The role of HA in a variety of respiratory diseases has also been investigated by several groups. found that HA binds to elastic fibers, preventing elastolysis and limiting airspace enlargement in experimental models of emphysema induced by elastases. Forteza et al. (8) proposed that HA plays a major role in mucosal host defense by stimulating ciliary beating via the RHAMM. Because HA is secreted into the alveolar subphase by type II cells (9,10), it has been suggested that it may interact with lung surfactant (11).Our previous work has shown that adding HA to different lung surfactants improved the surface activity and decreased surfactant inactivation caused by serum (12). In this study, we investigated the effects of using HA Survanta mixtures i...

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“…NMR spectroscopy allowed the proposal of an hydrogen bond network to describe the conformation of HA in aqueous solution and its interactions with water molecules. [22][23][24][25][26] In order to gather more information on this hydrogen bond network we utilized IR spectroscopy to follow the hydration of HA by water vapor, starting from dry films several microns thick in order to prevent any saturation of bands, particularly, when these films were later hydrated. In order to carry out such a program, we repeated the procedure for the hydration of BSA.…”

Section: Introductionmentioning

confidence: 99%

Hydration of polysaccharide hyaluronan observed by IR spectrometry. I. Preliminary experiments and band assignments

Haxaire¹,

Maréchal²,

Milas³

et al. 2002

Biopolymers

193

152

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This article is the first one in a series dedicated to the study of hyaluronan as observed by IR spectrometry. The goal is to determine its hydration mechanism and the structural changes this mechanism implies. Hyaluronan is a natural polysaccharide that is widely used in biomedical applications and cosmetics. Its macroscopic properties are significantly dependent on its degree of hydration. In this article we record the IR spectrum of a several micron thick dried film and deduce that four or five residual H 2 O molecules remain around each disaccharide repeat unit in the dried film. We then compare the spectra of sodium hyaluronan and its acid form to assign vibrational bands linked to the carboxylate group. We proceed with a qualitative analysis of the spectral changes induced by changes of temperature and hygroscopicity, two independent parameters that act by modifying the hydrogen bond network of the sample. This enables us to assign most of the vibrational bands of the hydrophilic groups and to distinguish the bands that are due to these hydrophilic groups when they are or are not hydrogen bonded. It constitutes a prerequisite for the quantitative analysis of hydration spectra that will be described in the following articles of this series.

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A water molecule participates in the secondary structure of hyaluronan

Cited by 129 publications

References 15 publications

Secondary and tertiary structures involving chondroitin and chondroitin sulphates in solution, investigated by rotary shadowing/electron microscopy and computer simulation

Secondary and tertiary structures involving chondroitin and chondroitin sulphates in solution, investigated by rotary shadowing/electron microscopy and computer simulation

Hyaluronan Reduces Surfactant Inhibition and Improves Rat Lung Function after Meconium Injury

Hydration of polysaccharide hyaluronan observed by IR spectrometry. I. Preliminary experiments and band assignments

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