A Simpler, Safer Synthetic Heparin

A Simpler, Safer Synthetic Heparin A team of researchers at the University of North Carolina at Chapel Hill and the Rensselaer Polytechnic Institute has created a simplified version of heparin, the widely used anticoagulent. The new version of heparin requires drastically fewer steps to produce than the only synthetic heparin on the market. The Process Starting disaccharide + Cofactors Researchers start with a two- Cofactors are "helper molecules."They are nonprotein chemical compounds that assist enzymes in biochemical transforma- tions. In this case, three cofactors help transform the starting disaccharide into heparin molecules: sugar molecule extracted from bacteria. UDP-GICNTFA Adds sugar molecules to the starting disaccharide UDP-GICA Enzymes Adds sugar molecules to the starting disaccharide Enzymes use molecules from the cofactors to elongate the starting disaccharide. PABS Adds sulfate molecules to the starting disaccharide Heparin molecule Unlike natural heparin, which has very large molecules, this synthetic heparin contains only the fragment that provides the anticoagulent properties. Graphics not to scale The Advantages Efficiency Safety Natural heparin is extracted from the tissues of cows or pigs, Synthetic heparin has traditionally been difficult to produce in large amounts, resulting in expensive therapies that are not widely used. While the actual manufacturing cost of this new heparin is not yet known, its simpler structure means it can be produced in significantly fewer steps than Fondaparinux, the only synthetic heparin currently on the market. a process susceptible to contamination. In 2008, a batch of contaminated heparin caused eighty- one deaths and hundreds of 10 < 50 other adverse reactions, leading to a recall of the drug. The cause was traced to a contaminant in the raw natural heparin extracted from pig intestines in China, Number of steps to produce the synthetic heparin created by the team at UNC and RPI Number of steps to produce the only version of synthetic heparin on the market Synthetic heparin is less susceptible to contami- nation during production. Also, the simplified version of heparin created at UNC and RPI does not contain the parts of the molecule that can cause dangerous side effects. Heparin: A Primer Commonly Used to Discovered in • Prevent or treat certain blood vessel, heart, and lung conditions • Prevent blood clotting during open-heart surgery, bypass surgery, kidney dialysis, and blood transfusions • Prevent the formation of blood clots in certain patients 1916 Making it one of the oldest drugs currently in widespread clinical use Cost for a 30-to-40 milligram dose Estimated Annual Sales $25-$35 $50-$60 $4,000,000,000 For low molecular weight heparin, a more refined version of natural heparin For Fondaparinux, the only synthetic heparin on the market Sources: UNC Eshelman School of Pharmacy, FDA.gov, Wikipedia The Scientists The research team that created the new synthetic heparin is led by Jian Liu, Ph.D., a professor at the UNC Eshelman School of Pharmacy, and Robert J. Lindhardt, the Ann and John H. Broadbent Jr. '59 Senior Constellation Professor at the Rensselaer Polytechnic Institute. The other authors of the study from the UNC Eshelman School of Pharmacy are postdoctoral research associates Yongmei Xu, Ph.D., and Renpeng Liu, Ph.D.; Haoming Xu, a UNC sophomore majoring in biochemistry; and first-year pharmacy student Juliana Jing. Additional authors are Sayaka Masuko of RPI and Madje Takieddin and Shaker Mousa, Ph.D., M.B.A., of the Albany College of Pharmacy and Health Sciences. Liu Lindhardt ILL UNC More Information ESHELMAN http://pharmacy.unc.edu/heparin2011 SCHOOL OF PHARMACY