Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

UNC scientists teach enzyme to make synthetic heparin in more varieties

28.11.2008
Scientists at the University of North Carolina at Chapel Hill have learned to customize a key human enzyme responsible for producing heparin, opening the door to a more effective synthetic anticoagulant as well as treatments for other conditions.

Jian Liu, Ph.D., and colleagues at the UNC Eshelman School of Pharmacy have learned to modify the enzyme heparan sulfate 2-O-sulfotransferase, which produces heparin in the human body in addition to other heparin-like molecules. By modifying 2-O-sulfotransferase, researchers will be able to create customized forms of synthetic heparin with different properties.

“Previously it was nearly impossible to change the nature of the heparin generated by the enzyme,” said Liu, associate professor in the school’s medicinal chemistry and natural products division. “The degree of difficulty was 10-plus. Now it’s more like a two or three, which opens the door to the possibility of improving on the natural product.”

Heparin is produced naturally by many creatures, including humans. As a drug, it is a common anticoagulant derived mainly from the intestinal lining of pigs. The manufactured form of the substance is most often used during and after procedures such as kidney dialysis, heart bypass surgery, stent implantation, indwelling catheters, and knee and hip replacements to prevent clots from blocking or restricting the flow of blood. The annual worldwide sales of heparin are estimated at $3 billion.

The drug was in the spotlight earlier this year when more than 80 people died and hundreds of others suffered adverse reactions to it, leading to recalls of the drug in countries around the world. Authorities linked the problems to a contaminant in raw natural heparin made from pigs in China. A synthetic version of the drug that can be produced in controlled conditions is key to preventing a recurrence of that tragedy, Liu said.

“The pig stuff has served us well for 50 years and is very inexpensive, but if we cannot control the supply chain, we cannot ensure the safety of the drug,” Liu said. “I am working for the day when synthetic heparin can be brewed in large laboratories at a low cost.”

There is also interest in heparin as a treatment for small-cell lung cancer, Liu said. Being able to produce customized versions of the heparin molecule using 2-O-sulfotransferase would allow researchers to emphasize the drug’s potential anti-cancer properties. Heparin-like structures have also shown potential as treatments for arthritis, asthma and transplant rejection, among other conditions.

An article describing these findings, “Redirecting the substrate specificity of heparan sulfate 2-O-sulfotransferase by structurally guided mutagenesis,” was recently published online in the journal Proceedings of the National Academy of Sciences. The study was supported by grants from the American Heart Association, the National Institutes of Health and the Intramural Research Program of the National Institute of Environmental Heath Sciences.

Liu is senior author of the study along with Lars Pedersen, Ph.D., an adjunct associate professor at the school and a staff scientist at the National Institute of Environmental Health Sciences. Other authors are Heather Bethea, Ph.D. candidate, and Ding Xu, Ph.D., a Ph.D student at UNC at the time of the study who is now a postdoctoral fellow at the University of California, San Diego.

Working with researchers from Rensselaer Polytechnic Institute, Liu developed a process to create commercially viable quantities of synthetic heparin in 2006. In 2007 he developed Recomparin, a variety of synthetic heparin with a simplified chemical structure that makes it easier to produce and perhaps less likely to cause side effects.

Patric Lane | EurekAlert!
Further information:
http://www.unc.edu

More articles from Life Sciences:

nachricht A novel socio-ecological approach helps identifying suitable wolf habitats
17.02.2017 | Universität Zürich

nachricht New, ultra-flexible probes form reliable, scar-free integration with the brain
16.02.2017 | University of Texas at Austin

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Switched-on DNA

20.02.2017 | Materials Sciences

Second cause of hidden hearing loss identified

20.02.2017 | Health and Medicine

Prospect for more effective treatment of nerve pain

20.02.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>