Jian Liu, PhD

Associate Professor

Division of Medicinal Chemistry
and Natural Products

Research Interests

Identification of polysaccharide-based receptor; structure and specificity of a heparan sulfate-based herpes simplex virus 1 receptor; drug targeting; gene therapy.

The blood-thinner heparin is one of the world’s best-selling drugs. It is also a difficult drug to produce consistently because it is a naturally occurring substance extracted from animal organs.

However, Jian Liu, PhD, and his colleagues at the UNC School of Pharmacy and Rensselaer Polytechnic Institute have discovered a solution to the difficulty of extracting heparin: make your own.

More Is Better

Heparin is most commonly used during and after procedures such 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.

Researchers at MIT were the first to develop a process for producing synthetic heparin, but they were only able to produce it in amounts less than one microgram (one human dose of heparin is approximately 100 milligrams). Liu and his colleagues, however, synthesized hundreds of milligrams of heparin by developing a large-scale process involving engineered enzymes and co-factor recycling.

“Synthesizing heparin chemically is extremely difficult, but by doing so, we eliminate the risk of viruses and other forms of contamination and improve the safety of a widely used drug,” says Liu, an associate professor at the School. “It gives us a cleaner compound. Our process mimics the existing process of extracting heparin from animal organs, so the synthetic version has very similar anticoagulant effect and can be metabolized in the body to maintain low drug toxicity.”

The researchers say their new, scaleable process can be applied to synthesize other heparin-based structures for regulating cell growth and may have applications in wound healing or cancer treatment. The process can also be used as a tool for screening lead compounds with heparin-like structures for drug discovery.

Research in Liu’s group in the School’s Division of Medicinal Chemistry and Natural Products focuses on the study of sulfated carbohydrates like heparin. Using recombinant biosynthetic enzymes, researchers design the structure of heparin to improve the anticoagulant activity and explore the antiviral and anticancer activities.

Liu collaborated on the interdisciplinary project with Robert Linhardt, a professor of biocatalysis and metabolic engineering at Rensselaer Polytechnic Institute. UNC-Chapel Hill and Rensselaer have jointly filed a provisional patent on the process.

Less Is Better

In 2007, Liu and his colleagues made another big stride in making heparin easier to produce. They created a synthetic version of the drug, Recomparin, that has a simpler chemical structure. They removed a complex component, a single sugar called iduronic acid that is difficult to replicate, from the heparin molecule without altering the drug’s function as an anticoagulant.

“We proved we don’t really need that structure for the anticoagulant effect,” Liu said. “By eliminating the iduronic acid unit, we were able to reduce the structural complexity of the heparin molecule by approximately 50 percent.”

Recomparin is also expected to reduce dangerous side effects, such as uncontrolled bleeding, while providing the same benefits as naturally derived heparin.

The next step for Recomparin will be to find a company to license the drug and begin the process of getting approval from the Food and Drug Administration.