Featured Research

from universities, journals, and other organizations

Scientists Teach Enzyme To Make Synthetic Heparin In More Varieties

Date:
November 27, 2008
Source:
University of North Carolina at Chapel Hill
Summary:
Scientists 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.

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.

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.


Story Source:

The above story is based on materials provided by University of North Carolina at Chapel Hill. Note: Materials may be edited for content and length.


Journal Reference:

  1. Bethea et al. Redirecting the substrate specificity of heparan sulfate 2-O-sulfotransferase by structurally guided mutagenesis. Proceedings of the National Academy of Sciences, 2008; DOI: 10.1073/pnas.0806975105

Cite This Page:

University of North Carolina at Chapel Hill. "Scientists Teach Enzyme To Make Synthetic Heparin In More Varieties." ScienceDaily. ScienceDaily, 27 November 2008. <www.sciencedaily.com/releases/2008/11/081125132516.htm>.
University of North Carolina at Chapel Hill. (2008, November 27). Scientists Teach Enzyme To Make Synthetic Heparin In More Varieties. ScienceDaily. Retrieved September 2, 2014 from www.sciencedaily.com/releases/2008/11/081125132516.htm
University of North Carolina at Chapel Hill. "Scientists Teach Enzyme To Make Synthetic Heparin In More Varieties." ScienceDaily. www.sciencedaily.com/releases/2008/11/081125132516.htm (accessed September 2, 2014).

Share This




More Health & Medicine News

Tuesday, September 2, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Snack Attack: Study Says Action Movies Make You Snack More

Snack Attack: Study Says Action Movies Make You Snack More

Newsy (Sep. 2, 2014) You're more likely to gain weight while watching action flicks than you are watching other types of programming, says a new study published in JAMA. Video provided by Newsy
Powered by NewsLook.com
U.N. Says Ebola Travel Restrictions Will Cause Food Shortage

U.N. Says Ebola Travel Restrictions Will Cause Food Shortage

Newsy (Sep. 2, 2014) The U.N. says the problem is two-fold — quarantine zones and travel restrictions are limiting the movement of both people and food. Video provided by Newsy
Powered by NewsLook.com
Doctors Fear They're Losing Battle Against Ebola

Doctors Fear They're Losing Battle Against Ebola

AP (Sep. 2, 2014) As a third American missionary is confirmed to have contracted Ebola in Liberia, doctors on the ground in West Africa fear they're losing the battle against the outbreak. (Sept. 2) Video provided by AP
Powered by NewsLook.com
Tech Giants Bet on 3D Headsets for Gaming, Healthcare

Tech Giants Bet on 3D Headsets for Gaming, Healthcare

AFP (Sep. 2, 2014) When Facebook acquired the virtual reality hardware developer Oculus VR in March for $2 billion, CEO Mark Zuckerberg hailed the firm's technology as "a new communication platform." Duration: 02:24 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins