Structure and physicochemical characterisation of heparin

Heparin is a member of the heparan sulphate family of glycosaminoglycans, a linear polysaccharide with a complex sequence resulting from the action of post-polymerisation enzymes on a regular repeating disaccharide background. Its overall conformation is rod-like in solution as well as in the solid state, but the conformational fluctuations of iduronate residues give rise to considerable internal motion and variation in local three-dimensional structure. Structure/function relationships and their relation to sequence are still the subject of argument, but new methodologies to tackle the subject are emerging. Heparin as a therapeutic agent and as the object of research may be characterised by numerous physico-chemical techniques. These include chromatographic methods for measurement of molecular weight; a variety of spectroscopic techniques; separation methods for whole polysaccharides, as well as for oligo- and monosaccharides; and mass spectrometric methods for mapping and sequence analysis. The impetus provided by the discovery of heparin contamination with oversulphated chondroitin sulphate has been influential in bringing combinations of many old and new techniques into use to ensure that heparin is sufficiently consistent and pure to be used safely. Synthetic and semi-synthetic heparins are in development and may become reality in the relatively near future.