Sep. 11, 2000 ATHENS, Ga. -- Chemists at the University of Georgia have developed a new method of synthesizing the principal constituent units of Heparin, a widely used anti-coagulant that is thought to be involved in numerous biological processes with proteins.
Since Heparin (or its components) is involved with coagulation, growth factor activation and cell adhesion, the research could lead to novel ways to fight disease or improve human health.
Part of the research results were announced this week at the annual meeting of the American Chemical Association in Washington, D.C.
"We have been able to assemble six precursors of the 19 known disaccharides that make up Heparin. These precursors can be used either as donors or acceptors in assembling larger Heparin structures," said chemist Geert-Jan Boons of the University of Georgia's department of chemistry and the Complex Carbohydrate Research Center. "We are not the first to synthesize Heparin fragments, but we are the first to do it using this building-block approach. Our approach is unique in the sense that it can quickly give a vast array fragments."
Colleagues in the research at the University of Georgia are doctoral student Michael Haller and post-doctoral associate Hailong Jiao.
Heparin is a natural polysaccharide that has been used as a medical anti-coagulant for more than half a century. It is isolated commercially from beef lung and pork intestinal mucosa and was discovered some 80 years ago. Worldwide sales of Heparin are well over $2 billion a year. It must be delivered intravenously, though an oral version is in development. Heparin is extremely effective in preventing blood clots following surgery.
Heparin's value is not limited to its anti-coagulant properties, however. There's mounting evidence that Heparin is involved in a dazzling array of biological processes, making the determination of its structure-function relationships a prime target of science. As the Human Genome Project nears completion, researchers will be seeing more and more ways that proteins function and create--or prevent--disease. Many of the newly discovered proteins may interact with Heparin.
"Carbohydrates have enormous potential to carry information, and that's one of the reasons why they are so important," said Boons. "By putting their principal building blocks in different orders, you can have a vast array of different structures working with a huge number of proteins. We already know that some proteins require Heparin for biological activity."
The research of Boons, Haller and Jiao focuses on utilizing the disaccharide building blocks of Heparin in the synthesis of larger structures. Thus far, they have assembled six of the 19 known building blocks. The team is also rapidly refining the methods--developed in Boons's lab--by which they achieved the feat. In principal, Boons said, they should be able to synthesize 80 to 90 percent of the Heparin structures by assembling these building block into larger structures.
Heparin is a mixture of polysaccharides with different chain lengths. Thus it is neither practical nor desirable to produce synthetically an entire Heparin molecule. Furthermore, the sheer size of renders the task futile. More practically, however, an entire molecule simply isn't needed. Short fragment of Heparin itself turn on or off biological activity, and so researchers don't need more than fragments.
Ultimately, researchers should be able to obtain Heparin fragments to perform a quick screening to determine interactions with biologically and medically important proteins. At present, scientists know that Heparin is involved with biological processes, but they aren't quite sure how all the processes work, and they are quite certain that currently unknown processes take place.
When scientists learn precisely which kind of Heparin fragments bind with specific proteins, entirely new avenues of medical therapies could become available. For instance, since it is known that Heparin in involved in certain aspects of growth factor regulation and in cell adhesion, one or more Heparin fragments could be used to turn off the uncontrolled cell growth that causes cancer.
While the actual medical use of novel Heparin fragments is still some years away, the matching of the fragments to proteins is much nearer.
"We believe that in two years, we will be able to test larger fragments on proteins," said Boons. "By then, we should be able to synthesize any fragment of the 19 building blocks as well."
If the past 10 years has been the decade of genomics--the locating of genes and their functions--the next decade will likely be the golden age of functional genomics. By 2010, researchers will have a much better idea why certain genes turn on or off proteins in plants and animals.
The Complex Carbohydrate Research Center at UGA is one of only a handful of research institutions world-wide that is able to synthesize complex oligosaccharides because of the molecules' size and complexity.
"These Heparin fragments are very important, will likely be involved with drug development as learn more and more about diseases and ways to interfere with their progress," said Boons. "These biological pathways are very complex, but when we understand them, we'll have a much better opportunity to intervene. This is the Holy Grail of genetics--to understand what causes disease and then to be able to turn it off."
Other social bookmarking and sharing tools:
The above story is based on materials provided by University Of Georgia.
Note: Materials may be edited for content and length. For further information, please contact the source cited above.
Note: If no author is given, the source is cited instead.