Structure and Physicochemical Characterisation of Heparin

Abstract

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.

USP compendial methods for analysis of heparin: chromatographic determination of molecular weight distributions for heparin sodium

“…It is a linear non-uniform polymer consisting of alternating glucosamine and uronic acid monosaccharide residues and is highly sulfated [1]. Heparin sodium drug product (HP) used in medicine consists of chains with molecular weight (MW) ranging from under 5,000 to over 50,000 [2].…”

Regulation of Complement and Contact System Activation via C1 Inhibitor Potentiation and Factor XIIa Activity Modulation by Sulfated Glycans – Structure-Activity Relationships

“…This may be due to the high iduronic acid content of heparins, whereas chondroitin sulfates exclusively contain glucuronic acid. A unique feature of iduronic acid is its conformational flexibility, which is considered to be advantageous for interactions with biomolecules [57]. (2) CurS1 was as active as DexS-H having a 2.4 timer higher DS and PhyS2 (DS 1.48) was more active than DexS-L (DS 2.02) so that a linear β-1,3-glucan structure seems to be more suitable to form sandwich complexes than the highly branched α-1,6-glucan structure of dextrans.…”

“…(2) CurS1 was as active as DexS-H having a 2.4 timer higher DS and PhyS2 (DS 1.48) was more active than DexS-L (DS 2.02) so that a linear β-1,3-glucan structure seems to be more suitable to form sandwich complexes than the highly branched α-1,6-glucan structure of dextrans. (3) As indicated by the superiority of PhyS2 and PhyS3 over OSHep, the β-1,3-glucan structure is supposed to be also more favourable than that of heparins, whereby this could also be due to their homogenous composition, whereas heparins consist of a complex mixture of heterogeneous molecules [57]. (4) Among the algae-derived SG, the fucose-containing sulfated polysaccharides (syn.…”

Development and use of sulodexide in vascular diseases: implications for treatment

“…The combination of HP polydispersity and microheterogeneity makes this compound structurally very complex 8. HP shows the maximum degree and heterogeneity of sulfation both at uronic acid and at glucosamine, and is therefore the substance with the greatest number of negative charges known so far.…”