Chemistry & Chemical Biology
Researchers Create Largest Dose of Synthetic Heparin
Robert Linhardt has spent years stitching together minuscule carbohydrates to build a more pure and safer alternative to the commonly used and controversial blood thinner heparin. At this year’s national conference of the American Chemical Society, Linhardt, the Broadbent Professor of Biocatalysis and Metabolic Engineering, announced that his research team may have accomplished this task by building the first fully synthetic heparin. Their creation is the largest dose of heparin ever created in a lab.
Heparin, a blood thinner derived from the intestines of foreign livestock, made
headlines when a contaminated dose proved lethal, killing more than 80 patients around the world.
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 says. “Such levels of production are further down the road. We think that in five years, it is very possible that this drug could reach human clinical trials.”
Linhardt is currently working with Jonathan Dordick at Rensselaer, Jian Liu from UNC Chapel Hill, and Shaker Mousa from the Albany College of Pharmacy to create and evaluate the larger batches of the drug.