Molecular structure of hyaluronan: an introduction

Hyaluronan is an unbranched polysaccharide of repeating disaccharides consisting of d-glucuronic acid and N-acetyl-d-glucosamine. Its strong water-retaining ability and visco-elastic properties have been broadly utilized in medical applications. Hyaluronan is an important constituent of the extracellular matrix whose physiological functions are manifested both as the substance is by itself as well as when it is being linked to various proteins. Compared with other biopolymers, such as nucleic acids and proteins, the structural chemistry of hyaluronan is much less developed. The scarce information about the metrical aspects of its structure shows no unusual features. Its secondary structure is characterized by intramolecular hydrogen bonding that is hard to distinguish from hydrogen bonding involving water molecules when hyaluronan is in aqueous medium. The tertiary structure of hyaluronan is sensitively dependent on its environment. The relative rigidity of the glycosidic bond and the intramolecular hydrogen bonds would tend to restrict rotational freedom and thus conformational variability. This, however, seems to be overwritten by the impact of molecular environment leading to a great variability of tertiary structure. A large number of conformations are possible and may be present as witnessed by their rather small free energy differences. Of the plethora of physical techniques and computational methods, X-ray crystallography and molecular dynamics calculations have proved to be the most fruitful so far. There are untapped possibilities in NMR spectroscopy for structural studies and quantum chemical calculations are also expected to contribute substantially to the structural chemistry of hyaluronan. There are many basic data as well as structural intricacies of hyaluronan that have so far eluded the researchers of its molecular structure. Dedicated to Endre A. Balazs, pioneer in hyaluronan research.