Thursday, March 27, 2014
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Synthetic low molecular
weight heparins (LMWHs) with
reversible and high anticoagulation activity
Synthetic LMWHs that have
low production costs and high sensitivity to the heparin antidote protamine could be useful for
treating thrombosis with enhanced safety and reduced cost. Current LMWH used
to treat and prevent thrombosis has issues including impurities, partial
reversibility and high production costs. A chemoenzymatic approach was used
to synthesize a series of LMWHs with varying numbers of iduronic acid or
glucuronic acid sugar units plus glucosamine and different sulfation
patterns. In mice, the lead LMWH had anticoagulant activity and showed liver
clearance rates and protamine sensitivity that were comparable to or higher
than those for marketed heparin products. Next steps include decreasing the number
of synthetic steps and improving the production of various enzymes and
cofactors used to synthesize the LMWH.
Published online March 27, 2014
application filed; licensing discussions under way with an undisclosed
Xu, Y. et al. Nat. Chem.
Biol.; published online Feb. 23, 2014;
Contact: Jian Liu, UNC Eshelman School of Pharmacy, Chapel
Contact: Robert J. Linhardt, Rensselaer Polytechnic
Institute, Rochester, N.Y.
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