Heparin (left) is an oligosaccharide bound to a very specific protein to form heparin proteoglycan. The physiologically important oligosaccharide is called heparan sulfate. It is found on the surface of normal endothelial cells and it is this molecule that binds antithrombin III. The interaction of heparan sulfate and antithrombin III inhibits blood clotting [Inhibiting Blood Clots: Anticoagulants].
It is very difficult to synthesize heparan sulfate so the synthetic drug is quite expensive. The results of a number of studies indicated that the exact structure of each of the sugar residues (rings) was very important for proper anticoagulant activity as was the position of the sulfate groups (those with "S" that are bound to the rings).
A recent paper by Chen et al. (2007) shows that simpler forms of the heparin-like oligosaccharide have significant anticoagulation activity. They started with a compound called N-sulfo heparosan, which is prepared from bacterial oligosaccharides by a combination of enzymatic and chemical steps. This starting material was then modified using various recombinant enzymes to produce a large class of heparin-like molecules. One of these derivatives, recomparin (below left) (Lindhardt and Kim, 2007) had significant anticoagulation activity. (Click on the figure to enlarge.)
The result is significant because recomparin does not have the modified rearranged sugar (iduronic acid, IdoUA)that was previously thought to be essential for anticoagulation activity. The modification of the oligosacchraide to create the iduronic acid residues was complicated an inefficient. Thus, the new recomparin drug will be much cheaper to make.
Chen, J., Jones, C.L. and Liu, J. (2007) Using an Enzymatic Combinatorial Approach to Identify Anticoagulant Heparan Sulfate Structures. Chemistry & Biology 14: 972-973.
Lindhardt, R.J. and Kim, J-H. (2007) Combinatorial Enzymatic Synthesis of Heparan Sulfate (review of Chen et al. 2007). Chemistry & Biology 14:972-973.