Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

UGA scientists team up to define first-ever sequence of biologically important carbohydrate

19.10.2011
Finding has implications for drug development as well as diseases such as cancer

If genes provide the blueprint for life and proteins are the machines that do much of the work for cells, then carbohydrates that are linked to proteins are among the tools that enable cells to communicate with the outside world and each other. But until now, scientists have been unable to determine the structure of a biologically important so-called GAG proteoglycan-or even to agree whether these remarkably complex molecules have well-defined structures.

In a paper published in the early online edition of the journal Nature Chemical Biology, however, a team of scientists from the University of Georgia and Rensselaer Polytechnic Institute announced that it has, for the first time, determined the sequence and structure of a glycosaminoglycan, or GAG, proteoglycan.

"The fact that a structure even exists is surprising, because people had the sense that the complexity of these molecules pointed to a randomness," said study co-author Jonathan Amster, professor and head of the department of chemistry in the UGA Franklin College of Arts and Sciences. "There are many different areas in medicine that will be enabled by understanding carbohydrates at this fundamental level."

Modifications to the GAG, or carbohydrate biopolymer, portion of proteoglycans have been associated with the presence and malignancy of certain cancers, for example, and the researchers noted that the identification of carbohydrates that are involved in disease opens the door to the development of drugs that can block their action.

The field of glycobiology is still in its infancy, largely because attempts to sequence proteoglycans have, until now, ended in frustration and failure. A small sample of DNA can be amplified many times, and its sequence, or arrangement of molecules, can be determined quickly with modern tools. DNA is simply a set of instructions for making proteins, so a sample of DNA also can allow scientists to produce copious quantities of protein for study.

Carbohydrates, however, are a bit messier. Scientists don't fully understand how cells create them, and a given proteoglycan exists in multiple forms that are similar but not quite the same.

The researchers chose the simplest known GAG proteoglycan, a compound known as bikunin that is used in Japan for the treatment of acute pancreatitis, for their study. Of course, simplicity is a relative term: the sugar is composed of up to 55 distinct carbohydrate rings, which means that there are 210 billion different sequence possibilities. Previous studies performed over the past five years by the researchers that identified common sequences within the carbohydrate decreased the expected number of sequences to a mere 43 million.

Past attempts to sequence proteoglycans have relied on the so-called "bottom up" approach in which scientists use enzymes to chop a molecule into its component parts and then try to put it back together, like a puzzle. Using an alternative approach known as the "top down" method, the scientists placed the compound into high-powered mass spectrometers in both the Amster and Linhardt labs that allowed them to break the compound in predictable places. With larger puzzle pieces to work with, the scientists were able to deduce the structure of bikunin.

"Now that we have demonstrated that bikunin, a small chondroitin sulfate proteoglycan, has sequence, we are moving on to larger, more structurally complex dermatan sulfate and heparan sulfate proteoglycans," said study co-author Robert Linhardt, professor at Rensselaer Polytechnic Institute. "These show important biological activities in development and in cancer, and we are optimistic that our sequencing approach will work here as well."

Like all groundbreaking scientific discoveries, the finding actually raises more questions than it answers. Amster explained that the addition of sulfate to the sugar, for example, could in principle occur anywhere along the carbohydrate chain. What the researchers found, however, was that the sites of sulfation occur only in particular rings. "That was the unexpected finding," Amster said, "because based on the current understanding of biology, there is no known mechanism for controlling that type of specificity."

As they work to determine the structure of more complex proteoglycans, the scientists hope that their findings will encourage other researchers to consider the role that they play in health.

"We know that carbohydrates are how cells communicate with each other and their environment, but they're also likely to play many roles that we can't even envision yet," Amster said. "And in order to understand them, we need to be able to study them at this molecular level."

In addition to Amster and Linhardt, additional authors include Mellisa Ly and Tatiana Laremore from Rensselaer Polytechnic Institute, Franklin Leach from UGA, and Toshihiko Toida from Chiba University in Japan.

The study was funded by the Institute of General Medical Sciences of the National Institutes of Health.

Sam Fahmy | EurekAlert!
Further information:
http://www.uga.edu

More articles from Life Sciences:

nachricht If Machines Could Smell ...
19.07.2019 | Fraunhofer-Institut für Produktionstechnik und Automatisierung IPA

nachricht Algae-killing viruses spur nutrient recycling in oceans
18.07.2019 | Rutgers University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Better thermal conductivity by adjusting the arrangement of atoms

Adjusting the thermal conductivity of materials is one of the challenges nanoscience is currently facing. Together with colleagues from the Netherlands and Spain, researchers from the University of Basel have shown that the atomic vibrations that determine heat generation in nanowires can be controlled through the arrangement of atoms alone. The scientists will publish the results shortly in the journal Nano Letters.

In the electronics and computer industry, components are becoming ever smaller and more powerful. However, there are problems with the heat generation. It is...

Im Focus: First-ever visualizations of electrical gating effects on electronic structure

Scientists have visualised the electronic structure in a microelectronic device for the first time, opening up opportunities for finely-tuned high performance electronic devices.

Physicists from the University of Warwick and the University of Washington have developed a technique to measure the energy and momentum of electrons in...

Im Focus: Megakaryocytes act as „bouncers“ restraining cell migration in the bone marrow

Scientists at the University Würzburg and University Hospital of Würzburg found that megakaryocytes act as “bouncers” and thus modulate bone marrow niche properties and cell migration dynamics. The study was published in July in the Journal “Haematologica”.

Hematopoiesis is the process of forming blood cells, which occurs predominantly in the bone marrow. The bone marrow produces all types of blood cells: red...

Im Focus: Artificial neural network resolves puzzles from condensed matter physics: Which is the perfect quantum theory?

For some phenomena in quantum many-body physics several competing theories exist. But which of them describes a quantum phenomenon best? A team of researchers from the Technical University of Munich (TUM) and Harvard University in the United States has now successfully deployed artificial neural networks for image analysis of quantum systems.

Is that a dog or a cat? Such a classification is a prime example of machine learning: artificial neural networks can be trained to analyze images by looking...

Im Focus: Extremely hard yet metallically conductive: Bayreuth researchers develop novel material with high-tech prospects

An international research group led by scientists from the University of Bayreuth has produced a previously unknown material: Rhenium nitride pernitride. Thanks to combining properties that were previously considered incompatible, it looks set to become highly attractive for technological applications. Indeed, it is a super-hard metallic conductor that can withstand extremely high pressures like a diamond. A process now developed in Bayreuth opens up the possibility of producing rhenium nitride pernitride and other technologically interesting materials in sufficiently large quantity for their properties characterisation. The new findings are presented in "Nature Communications".

The possibility of finding a compound that was metallically conductive, super-hard, and ultra-incompressible was long considered unlikely in science. It was...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on UV LED Technologies & Applications – ICULTA 2020 | Call for Abstracts

24.06.2019 | Event News

SEMANTiCS 2019 brings together industry leaders and data scientists in Karlsruhe

29.04.2019 | Event News

Revered mathematicians and computer scientists converge with 200 young researchers in Heidelberg!

17.04.2019 | Event News

 
Latest News

Heat flow through single molecules detected

19.07.2019 | Physics and Astronomy

Heat transport through single molecules

19.07.2019 | Physics and Astronomy

Welcome Committee for Comets

19.07.2019 | Earth Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>