Depolymerization of Heparin/HS

Heparin and heparan sulfate (HS) glycosaminoglycans are linear sulfated polysaccharides located on cell-surface membranes and in extracellular matrices in virtually all animal tissues. Heparin and HS have been implicated in cell-biological processes, cell adhesion and regulation of enzymatic catalysis (1). HS chains have been shown to interact with a variety of growth factors, chemokines, extracellular matrix proteins, and enzymes, including antithrombin, fibroblast growth factors, and vascular endothelial growth factor (2) as shown by choosing the tab below. Heparin has been widely used as an anticoagulant drug (3,4), and it has been shown to regulate cellular process by binding, stabilizing and activating various growth factors (5).


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  2. Linhardt, R. J., et al. (1990) Biochemistry 29(10), 2611-2617. PMID: 2334685
  3. Linhardt, R. J. and Gunay, N. S. (1999) Semin. Thromb. Hemost. 25 Suppl. 3, 5-16. PMID: 10549711
  4. Casu, B., et al. (2002) Biochemistry 41(33), 10519-10528. PMID: 12173939
  5. Knudsen, C. B., Knudsen, W. (2001) Semin. Cell. Dev. Biol. 12, 69-78. PMID: 11292372
  6. Ilan N, Elkin M, Vlodavsky I. (2006) Int. J. Biochem. Cell. Biol. 38(12), 2018-39. PMID: 16901744
  7. Rosen SD, Lemjabbar-Alaoui H. (2010) Expert Opin. Ther. Targets. 14(9), 935-49. PMID: 20629619

Depolymerization of Heparin/HS includes these areas of focus:

MS Analysis of GAGs

HS chain interactions

Membrane bound proteoglycan (syndecan) showing heparan sulfate chains binding to vascular endothelial growth factor (VEGF). Highly sulfated domains bind free VEGF, creating a morphogen gradient, and thus facilitating binding to its receptor in the plasma membrane. Heparin-bound VEGF is released upon desulfation by sulfatases. Alternatively, active heparin fragments are shed by heparinases. These mechanisms are critical during blood vessel morphogenesis, particularly in tumor proliferation (6,7).