Heparins

Heparin Polymers, Oligosaccharides, Desulphated Polymers and Oligosaccharides

Heparin is a highly sulfated glycosaminoglycan predominantly localized within mast cell granules. While its primary clinical application is as an anticoagulant, its interactions with a broad spectrum of effector proteins have highlighted its potential in diverse pathological and therapeutic contexts.

We provide high-purity, research-grade heparin, alongside a comprehensive range of heparin polymers and oligosaccharides varying in molecular weight and sulfation patterns. These structurally distinct polymers facilitate the investigation of key biochemical and biophysical properties underpinning heparin’s biological activity. Such studies are essential for elucidating structure-function relationships and advancing its potential applications in drug development, regenerative medicine, and cellular signaling.

Our products are designed to support cutting-edge research in glycoscience, pharmacology, and biomedical engineering.

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.

Product Descriptions and References

Heparin and Low Molecular Weight Heparin

Heparin (cat # HEP001) has an average molecular weight of about 15 kDa it is highly polydisperse with a considerable spread of mol wts.

LMW Heparin is made via partial digestion of heparin with heparinase I, it is less polydisperse than the heparin it is made from (HEP001) with a molecular weight range of 1800 – 7500 daltons.

References

1. Vögtle, T., Sharma, S., Mori, J., Nagy, Z., and Semeniak, D. (2019). Heparan sulfates are critical regulators of the inhibitory megakaryocyte-platelet receptor G6b-B. eLife, [online] Available at: https://elifesciences.org/articles/46840 [Accessed 11 Mar. 2025].

2. Verespy, S. and Gordts, L.S.M. (2018). Efficient synthesis of heparinoid bioconjugates for tailoring FGF2 activity at the stem cell-matrix interface. Scholar Archive, [online] Available at: https://scholar.archive.org/work/yxvmj43m7fezthq3ypgz3pdufi/access/wayback/https://s3-eu-west-1.amazonaws.com/itempdf74155353254prod/7522784/Efficient_Synthesis_of_Heparinoid_Bioconjugates_for_Tailoring_FGF2_Activity_at_the_Stem_Cell-Matrix_Interface_v1.pdf [Accessed 11 Mar. 2025].

Selectively Desulfated Heparin Polymers

Our selectively desulfated heparin polymers are prepared using precise, site-selective chemical desulfation methods, targeting specific sulfate groups within the heparin structure. These modifications include:

N-desulfation (N-deS): Removal of sulfate groups from the amino position (N-sulfate) of glucosamine.

2-O-desulfation (2-O-deS): Selective removal of sulfate groups from the C2 position of uronic acid.

6-O-desulfation (6-O-deS): Removal of sulfate groups from the C6 position of glucosamine.

N-desulfated, re-N-acetylated heparin (N-deS/Ac): Following N-desulfation, the free amino group is acetylated, altering its biochemical properties.

These selectively modified heparin derivatives serve as essential tools for studying the impact of specific sulfate groups on heparin’s conformation, molecular interactions, and binding properties. They provide valuable insights into heparin-protein interactions, anticoagulant activity, and receptor binding dynamics, supporting research in glycoscience, drug development, and biomedical applications.

Publications

1. Townsend, D., Fullwood, N.J., and Yates, E.A. (2020). Aggregation kinetics and filament structure of a tau fragment are influenced by the sulfation pattern of the cofactor heparin. Biochemistry, [online] Available at: https://pubs.acs.org/doi/abs/1... [Accessed 11 Mar. 2025].

2. Yap, L., Murali, S., Bhakta, G., and Titmarsh, D.M. (2018). Immobilization of vitronectin-binding heparan sulfates onto surfaces to support human pluripotent stem cells. Journal of Biomedical Materials Research Part B: Applied Biomaterials, [online] Available at: https://espace.library.uq.edu.au/view/UQ:d2ced77/UQd2ced77_OA.pdf [Accessed 11 Mar. 2025].

3. Raman, K., Mencio, C., and Desai, U.R. (2013). Sulfation patterns determine cellular internalization of heparin-like polysaccharides. Molecular Pharmaceutics, [online] Available at: https://pubs.acs.org/doi/abs/1... [Accessed 11 Mar. 2025].

Heparin Oligosaccharides

Heparin oligosaccharides are generated through the controlled partial depolymerization of heparin via Heparinase I, followed by high-resolution gel filtration to separate the resulting oligosaccharides.

General Formula:

UA,2S – (GlcNS,6S – IdoA,2S)ₙ=1-9 – GlcNS,6S

(Note: The uronic acid at the non-reducing end of the chain contains a C4-C5 double bond due to the endolytic activity of Heparinase I.)

While the predominant disaccharide unit in heparin is the trisulfated GlcNS,6S – IdoA,2S (~65%), native heparin also comprises a heterogeneous mixture of di-, mono-, and non-sulfated saccharide units. As a result, each oligosaccharide size fraction, although largely homogeneous in molecular weight, exhibits variability in sulfation content and pattern.

In the product list below, dp (degree of polymerization) denotes the number of monosaccharide units. For example:

dp4 (HO04): Tetrasaccharide

dp6 (HO06): Hexasaccharide

dp8 (HO08): Octasaccharide

(and so forth)

These well-characterized heparin oligosaccharides serve as critical tools for investigating the structural determinants of heparin’s biological function, including its interactions with proteins, receptors, and cellular systems.

Publications 

1. Sargison, L. (2023). Modified Heparins for Bone Repair. Victoria University of Wellington. Available at: https://openaccess.wgtn.ac.nz/articles/thesis/Modified_Heparins_for_Bone_Repair/22943456 [Accessed 11 Mar. 2025].

2. Arnold, K. (2019). Application of Heparin and Heparan Sulfate Oligosaccharides Prepared by Chemoenzymatic Synthesis. University of North Carolina at Chapel Hill. Available at: https://cdr.lib.unc.edu/concer... [Accessed 11 Mar. 2025].

3. Liang, Q., Chopra, P., Boons, G.J. and Sharp, J.S. (2018). Improved de novo sequencing of heparin/heparan sulfate oligosaccharides by propionylation of sites of sulfation. Carbohydrate Research, [online] Available at: https://www.sciencedirect.com/science/article/pii/S0008621518302611 [Accessed 11 Mar. 2025].

1. Zhang, F., Yang, B., Ly, M., Solakyildirim, K. and Xiao, Z. (2011). Structural characterization of heparins from different commercial sources. Analytical and Bioanalytical Chemistry, [online] Available at: https://link.springer.com/article/10.1007/s00216-011-5367-7 [Accessed 11 Mar. 2025].

2. Bhaskar, U., Li, G., Fu, L., Onishi, A. and Suflita, M. (2015). Combinatorial one-pot chemoenzymatic synthesis of heparin. Carbohydrate Polymers, [online] Available at: https://www.sciencedirect.com/science/article/pii/S0144861714010662 [Accessed 11 Mar. 2025].

Selectively Desulfated Heparin Oligosaccharides

We offer a range of selectively desulfated heparin oligosaccharides, prepared through the controlled partial depolymerization of desulfated heparins using Heparinase enzymes, followed by high-resolution gel filtration for precise oligosaccharide separation.

Three distinct variations of selectively desulfated heparin oligosaccharides are available, covering molecular sizes from dp4 to dp12 (degree of polymerization, representing the number of monosaccharide units in each oligosaccharide):

2-O Desulphated Oligosaccharides: Sulfate group selectively removed from the C2 position of iduronate.

6-O Desulphated Oligosaccharides: Sulfate group selectively removed from the C6 position of glucosamine.

N-Desulphated reN Acetylated Oligosaccharides: The amino group in N desulphated heparin is modified through acetylation, altering functional properties.

For reference:

dp4 = tetrasaccharide

dp6 = hexasaccharide

dp8 = octasaccharide (and so on)

These site-selective desulfated oligosaccharides serve as essential tools for investigating the structure-function relationships of heparin, offering insights into protein interactions, receptor binding, and biological activity modulation. 

Publications 

1. Lin, J., Zheng, L., Liang, Q., Jiang, L., and Wei, Z. (2021). Preparation and characterization of partial de-O-sulfation of heparin oligosaccharide library. Carbohydrate Research, [online] Available at: https://www.sciencedirect.com/science/article/pii/S0008621520305978 [Accessed 11 Mar. 2025].

2. Ryan, E.O., Jiang, Z., Nguyen, H., and Wang, X. (2021). Interactions of pleiotrophin with a structurally defined heparin hexasaccharide. Biomolecules, 12(1), 50. [online] Available at: https://www.mdpi.com/2218-273X... [Accessed 11 Mar. 2025].

3. Alekseeva, A., Casu, B., Torri, G., Pierro, S., and Naggi, A. (2013). Profiling glycol-split heparins by high-performance liquid chromatography/mass spectrometry analysis of their heparinase-generated oligosaccharides. Analytica Chimica Acta, [online] Available at: https://www.sciencedirect.com/science/article/pii/S000326971200591X [Accessed 11 Mar. 2025].