Heparinases

Using high purity enzymes will provide reliable and reproductive results.

Glycosaminoglycans (GAGs) are large linear-unbranched polysaccharide chains with repeating disaccharide units of amino sugar (either GlcNAc or GalNAc) and an uronic acid (either glucuronic acid and/or iduronic acid). Five glycosaminoglycan chains were identified, viz., Hyaluronan, Chondroitin, Dermatan, Heparin/heparan and Keratan with possible sulfation at 2S, 4S or 6S locations.

In virtually all animal tissues, the cell membranes and the extracellular matrices (ECM) are decorated with glycosaminoglycans (GAGs) such as heparin and heparan sulfate (HS), which are linear sulfated polysaccharides. These GAGs play an intricate role in the ECM, as polyelectrolytes by specifically interacting with growth factors and other transient components of the ECM. Heparin and HS have been associated with cell-biological processes, cell adhesion and regulation of enzymatic catalysis while HS chains have been shown to interact with a variety of growth factors (fibroblast growth factors and vascular endothelial growth factor), chemokines, ECM proteins, enzymes, and antithrombin. Additionally, heparin and HS molecules were found to mediate the viral adhesion and the infection process and considered as important factors in the host-pathogen interactions.

Heparin has been widely used as an anticoagulant drug and it has been shown to regulate cellular process by binding, stabilizing and activating various growth factors. Furthermore, heparin is used in the production of low molecular weight and ultra-low molecular weight heparin molecules that are used as anticoagulant drugs with defined functionalities in which Heparinases or chemical modification processes are employed to cleave the heparin molecules. The catalytic targets of heparinase I, II and III are shown in the figure below.

OUR PRODUCTS

HEPARINASE I

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Heparinase I (EC 4.2.2.7) cleaves heparin and to a lesser extent, heparan sulfate. Available as Liquid (Frozen) or Lyophilized. Click the data sheets.pdf icons below for complete details.

Heparinase II

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Heparinase II (EC unassigned) cleaves both heparin and heparan sulfate. Available as Liquid (Frozen) or Lyophilized. Click data sheets below for complete details.

HEPARINASE III

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Heparinase III  (EC 4.2.2.8) cleaves heparan sulfate exclusively. Available as Liquid (Frozen) or Lyophilized. Click the data sheets.pdf icons below for complete details.

OVERVIEW

IBEX produces a family of high purity recombinant glycosaminoglycan (GAG) lyases; among them are Heparinase I, Heparinase II, Heparinase III, which are widely used in research, the production of low molecular weight heparin and ultra-low molecular weight heparins, and in conjunction with clinical diagnostic IVDs for hemostasis monitoring.

References

  1. Fritz, T. et al. (1994)  Biol. Chem.269, 28809-28814. PMID: 7759502
  2. Linhardt, R.J. et al. (1990) Biochemistry29, 2611-2617. PMID: 2334685
  3. Linhardt, R.J., and Gunay, N.S. (1999)  Thromb. Hemost. 25 Suppl 3, 5-16. PMID: 10549711
  4. Casu, B. et al. (2002) Biochemistry41, 10519-10528. PMID: 15106730
  5. Knudsen, C.B. and Knudsen, W. (2001) Cell Dev. Biol.12, 69-78. PMID: 11292372

IBEX has developed a proprietary Pedobacter heparinus (formerly Flavobacterium heparinum) expression system which unlike other heparinase expression systems produces glycosylated enzymes.

Competitor enzymes purified from the native strain of P. heparinus (formerly F. heparinum) will almost certainly contain cross-contaminants of other GAG enzymes.

Due to its high purity and reaction time, IBEX Heparinase I is the only heparinase used in FDA and EU approved hemostasis-measuring Point Of Care medical diagnostic devices.  IBEX high purity heparinases have proven to yield reproducible and reliable results with consistent performance.

The IBEX Pharmaceutical’s Quality Management System is certified ISO 13485:2016. for the manufacture and sale of protein reagents and reagent-filled medical diagnostic device components.