Heparan Sulphates

Heparan Sulphate - Guidance notes

Heparan sulphate (HS) is widely recognised as the major glycosaminoglycan on cell surfaces; it is an essential co-receptor for many growth factors, morphogenic proteins and signalling structural elements in the extracellular matrix such as fibronectin and various types of collagen. It has a distinctive molecular organisation in which sulphated domains are spaced along the polymer chain separated by regions that are largely devoid of sulphate groups. Despite sharing a common design the HS fine structure is often typical of the cell of origin due to variability of sulphation patterns in the sulphated regions. This variability probably underpins specific protein binding activities at cell surfaces.

Kjellen, L. and Lindahl, U. (2018) Specificity of glycosaminoglycan-protein interactions. Current Opinion in Structural Biology 50:101–108

Gallagher J. (2015) Fell-Muir Lecture: Heparan Sulphate and the art of cell regulation: a polymer chain conducts the protein orchestra. Int J Exp Pathol. 96:203-231.

Xu D. and  Esko JD: (2014) Demystifying heparan sulfate-protein interactions. Annu Rev Biochem . 83:129-157.

To assist investigations of this most intriguing of glycosaminoglycans we offer several preparations of Heparan Sulphates that vary in molecular size and sulphation including a unique set of selectively-desulphated Heparan Sulphates. Please also see our heparin oligosaccharides that mimic some of the sulphation variability seen in HS.

Heparan Sulphate Polymer Fractions

1. Heparan Sulphate fraction I: Mol wt approx. 40kDa

Relatively low in Sulphation (when compared to parent GAG-HS01)/High Molecular Weight HS.

40 N-sulphate groups per 100 disaccharides 35 O-sulphate groups per 100 disaccharides *Polymer sulphation (N- and O-sulphate groups) is 75 per 100 disaccharides. The domain structure of this preparation is broadly similar to the most common form of heparan sulphate present on cell surfaces

2. Heparan Sulphate fraction III: Mol wt approx. 9kDa

High Sulphate/Low Molecular Weight HS.

65 N-sulphate groups per 100 disaccharides 110 O-sulphate groups per 100 disaccharides *Polymer sulphation (N- and O-sulphate groups) is 175 per 100 disaccharide

3. Heparan Sulphate

Heparan Sulphate isolated from porcine mucosa. This material contains both high and low sulphated species of HS and gives a bimodal molecular weight profile with fractions of approx. 40kDa and 9kDa; the smaller of the two fractions is the more sulphated component. This preparation has been separated by preparative SAX-hplc to give the three HS fractions listed above.

Heparan Sulphate Oligoaccharides

Heparan Sulphate (HS) is a near-universal co-receptor for many growth factors and morphogenic proteins; it has a complex domain organisation of alternating high and low sulphated regions (Fig 1) in which the various patterns of modification by sulphation by and epimerisation create considerable structural diversity designed for selective binding to its many client proteins.