September 22, 2010
Jian Liu, PhD, has taken another step forward in his quest for a synthetic version of the drug heparin by improving the process of building the drug molecule’s backbone using chemically modified cofactors instead of natural cofactors.
Liu and colleagues at the UNC Eshelman School of Pharmacy outline their procedure in the article “Chemoenzymatic Design of Heparan Sulfate Oligosaccharides” published in the Journal of Biological Chemistry. Liu is working to perfect Recomparin, a man-made heparin replacement that he has developed.
“This is a milder, more efficient process,” Liu says. “It allows for a more precise structure that gives us a better yield when synthesizing molecules, which should result in lower production costs and higher quality in the future.”
The blood-thinner heparin is one of the world’s best-selling drugs, but it is also a difficult drug to produce consistently because it is a naturally occurring substance extracted from animal organs, primarily the intestinal lining of pigs. Liu and his colleagues were the first to synthesize a significant quantity of man-made heparin by developing a large-scale process involving engineered enzymes and co-factor recycling.
Liu is an associate professor in the Division of Medicinal Chemistry and Natural Products. His coauthors on the paper are Renpeng Liu, Yongmei Xu, Miao Chen, Xianxuan Zhou, and Qisheng Zhang, PhD, of the UNC Eshelman School of Pharmacy; Arlene S. Bridges, PhD, of the UNC School of Medicine; Paul L. DeAngelis, PhD, of the University of Oklahoma Health Sciences Center, and Robert J. Linhardt, PhD, and Michel Weïwer, PhD, of the Rensselaer Polytechnic Institute.
This work is supported in part by National Institutes of Health grants AI50050, HL094463, HL62244, HL096972 and GM38060 and by the grant-in-aid (0855424E) from the American Heart Association, MidAtlantic Affiliate.
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