Rensselaer Research ReviewWinter 2008
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Wayne G. Roberge
Rotation of the extended helix of heparin dodecasaccharide sequence by 90 degrees is shown in a space-filling representation with the charged sulfo groups shown as yellow balls with attached oxygen as red balls lying on the outer surface of the molecule.
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The “Recipe” for Heparin

Linhardt, together with Jian Liu of the University of North Carolina, discovered the synthetic “recipe” for heparin in 2006. Since that time he has worked to piece together the various molecules and grow a complex carbohydrate that is naturally created in the body in the lab. The carbohydrate backbone for the new heparin comes from the bacteria E. coli. The use of the common and easily grown bacteria makes this version of heparin much easier and faster to produce, according to Linhardt. The team used a process called chemoenzymatic synthesis that used specialized synthetic chemicals and natural enzymes expressed in E. coli to replicate the normal biosynthesis of natural heparin within the cell.

The dose that Linhardt and his team were able to produce with this method was a million times higher than any other alternative created to date. He will now continue to work with his partners to take the milligram dose that they have developed and expand it to kilograms. “Ultimately, drug companies are going to need to produce tons of this drug to keep up with global demand,” he said. “Such levels of productions are further down the road. We think that in five years, it is very possible that this drug could reach human clinical trials.” 

The milligram-scale synthesis of heparin will be published in the Journal of the American Chemical Society. To complete the research, Linhardt was joined by Zhenqung Zhang, Scott McCallum, and Jin Xie at Rensselaer; Lidia Nieto and Jesus Jimenez-Barbero at Centro de Investigaciones Biologicas; Francisco Corzana at Universidad de La Rioja UA-CSIC; and Miao Chen and Jian Liu at the University of North Carolina, Chapel Hill. He is currently working with Jonathan Dordick at Rensselaer and Jian Liu from Chapel Hill and Shaker Mousa from Albany College of Pharmacy to create and evaluate the larger batches of the drug.

 

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