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 Kidney tumor: Genetic trigger discovered
18.06.2018 | Julius-Maximilians-Universität Würzburg

nachricht New type of photosynthesis discovered
18.06.2018 | Imperial College London

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: AchemAsia 2019 will take place in Shanghai

Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.

Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...

Im Focus: First real-time test of Li-Fi utilization for the industrial Internet of Things

The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.

Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.

Im Focus: Sharp images with flexible fibers

An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.

Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...

Im Focus: Photoexcited graphene puzzle solved

A boost for graphene-based light detectors

Light detection and control lies at the heart of many modern device applications, such as smartphone cameras. Using graphene as a light-sensitive material for...

Im Focus: Water is not the same as water

Water molecules exist in two different forms with almost identical physical properties. For the first time, researchers have succeeded in separating the two forms to show that they can exhibit different chemical reactivities. These results were reported by researchers from the University of Basel and their colleagues in Hamburg in the scientific journal Nature Communications.

From a chemical perspective, water is a molecule in which a single oxygen atom is linked to two hydrogen atoms. It is less well known that water exists in two...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Munich conference on asteroid detection, tracking and defense

13.06.2018 | Event News

2nd International Baltic Earth Conference in Denmark: “The Baltic Sea region in Transition”

08.06.2018 | Event News

ISEKI_Food 2018: Conference with Holistic View of Food Production

05.06.2018 | Event News

 
Latest News

Novel method for investigating pore geometry in rocks

18.06.2018 | Earth Sciences

Diamond watch components

18.06.2018 | Process Engineering

New type of photosynthesis discovered

18.06.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>