March 2, 2009
Jian Liu, PhD, an associate professor in the Division of Medicinal Chemistry and Natural Products, has been awarded a four-year $1.48 million grant from the National Institutes of Health to further develop Recomparin, his synthetic version of the drug heparin.
Liu’s project is titled “In vitro synthesis of recombinant heparan sulfate.” Heparan sulfate is a compound produced in the body that is similar to heparin but has weaker anticoagulant properties. Heparin can be made from heparin sulfate, and by modifying the molecular structure of the heparan sulfate he produces, Liu can customize the properties of heparin derived from it.
Currently, synthetic forms of heparin are difficult to produce in large quantities because of the drug’s complexity, resulting in expensive medicines that are not widely used. The simpler structure of Recomparin is likely to be easier to produce than other forms of synthetic heparin, Liu says. He says he also expects Recomparin to reduce the dangerous side effects of natural heparin, such as uncontrolled bleeding and heparin-induced thrombocytopenia (too few platelets in the blood), while providing the same benefits as naturally derived heparin.
Heparin is most often used during and after such procedures as kidney dialysis, heart-bypass surgery, stent implantation, indwelling catheters, and knee and hip replacement to prevent clots from forming and blocking or restricting the flow of blood. The annual worldwide sales of heparin are estimated at $3 billion.
The drug was in the spotlight in spring 2008 when more than eighty people died and hundreds of others suffered adverse reactions to it, leading to recalls of heparin in countries around the world. Authorities linked the problems to a contaminant in raw natural heparin extracted from pig intestines in China. A synthetic version of the drug that can be produced in controlled conditions is the key to preventing a recurrence of that tragedy, Liu said.
Liu is collaborating on the project with Qisheng Zhang, PhD, an assistant professor at the School, and Robert Linhardt, PhD, the Ann and John H. Broadbent, Jr. ’59 Senior Constellation Professor of Biocatalysis and Metabolic Engineering at Rensselaer Polytechnic Institute. In 2006 Liu and Linhardt worked together to create the first viable method of producing large quantities of synthetic heparin.
The project described is supported by award number R01HL094463 from the National Heart, Lung, and Blood Institute of the NIH. The content of this announcement is solely the responsibility of the UNC Eshelman School of Pharmacy and does not represent the official views of the National Heart, Lung, and Blood Institute or the NIH.
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