Heparin - Guidance notes
Heparin is a highly-sulphated glycosaminoglycan found mainly in mast cell granules; it’s principal clinical use is as an anticoagulant but its reactivity with many effector proteins is leading to potential applications in a variety of human diseases. Heparin is chemically-related to heparan sulphate (HS), a common component of cell surfaces that plays key roles in the control of cell growth and development. Heparin, and oligosaccharides derived from heparin, can be used as functional analogues of the sulphated regions of HS but with the proviso that the high charge density of heparin may, in some instances, lack the discrimination of protein binding seen in the less sulphated HS. To some degree this limitation can be overcome by use of size-limited heparin saccharides and by the preparation of specifically-desulphated heparin derivatives, all available from Iduron and listed below; such key reagents can give valuable information on the structural elements necessary for the activity under study. If more in depth work is needed then data acquired using our heparin-based reagents can guide the selection of heparin and HS motifs in our extensive “HepMer” range of defined oligomeric sequences.
Page, C. (2013 Heparin and Related Drugs: beyond Antocoagulant Activity. ISRN Pharmacology, 2013; ID 910973
Cassinelli, G. and Naggi, A. (2016) Old and new applications of Non-Antocoagulant Heparin. Int. Cardiol. 21251: S14-S21
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.
Heparin and Low Molecular Weight Heparin
Heparin Polymer Molecular Weight (Mw) Series prepared from High Grade Unfractionated Heparin (UF)
These highly-purified, low polydispersity heparins were isolated from our High-Grade Heparin (Cat. No. HEP-HG 001; Mw 15,700) and cover the range of polymer chains present in unfractionated heparins.
Molecular weights were determined using the USP Heparin Sodium molecular weight calibrant for molecular weight measurement of unfractionated heparin.
Selectively Desulphated Heparin Polymers
These heparin products have been made from high quality heparin modified by standard chemical methods to selectively remove sulfate groups from C2 of Iduronate, (De2S Hep), C6 of glucosamine (De6SHep) or the N-sulfate of Glucosamine (DeNS Hep). The DeNS heparin contains the free amino group (NH+3); in DeNS/Ac Hep the free amino group has been modified by acetylation.
Prepared by controlled partial depolymerisation of UF heparin by Heparinase I and separation of the derived oligosaccharides using high resolution gel filtration. The products cover the entire range of oligosaccharides present in Low Molecular Weight Heparins. General formula:
*UA,2S – (GlcNS,6S – IdoA,2S) – GlcNS,6S
*the uronic acid at the non-reducing end of the chain contains a C4-C5 double bond due to the endolytic action of Heparinase I
Although the main disaccharide in heparin is the trisulphated unit GlcNS,6S – IdoA,2S heparin also contains di-, mono- and non-sulphated units; thus each size class of oligosaccharide, though substantially homogeneous in molecular size, contains structures that vary in content and pattern of sulphation. The 2mg amounts of supplied material can be subfractionated (eg. by SAX-hplc) for further analysis of naturally-occurring heparin sequences within a specific size class or classes.
Main Heparin Disaccharide Unit
Selectively Desulphated Heparin Oligosaccharides
Heparin oligosaccharides made by partial digestion of high quality heparin modified by standard chemical methods to selectively remove the sulphate groups.
Investigate the specific protein binding motifs in Heparin and HS GAGs. Use these products in conjunction with our heparin oligosaccharides and HepMers to investigate the essential functional groups and specific oligosaccharide chain length required for high affinity/optimal protein interactions.
4 variations of selectively desulphated heparin oligosaccharides are available, dp4 – dp12:
2-O-desulphated heparin oligosaccharides Sulphate group removed from the C2 of iduronate
6-O-desulphated heparin oligosaccharides Sulphate group removed from the C6 of glucosamine
N-desulphated heparin oligosaccharides Sulphate group removed from the N sulphate of the glucoasmine
N-desulphated re N-acetylated heparin oligosaccharides The free amino group (NH+3) in N-desulphated heparin has been modified by acetylation