A sweet step toward new cancer therapies

By recognizing sugars, a technique developed by University of Michigan analytical chemist Kristina Hakansson sets the stage for new cancer diagnosis and treatment options.

A growing body of evidence points to assemblies of sugars called glycans attached to proteins on cancer cell surfaces as accomplices in the growth and spread of tumors. Researchers have been keen to characterize these glycans, but traditional analytical methods have not been sufficient.

Now, Hakansson's research group has demonstrated that their technique can be used to identify and structurally characterize glycans. Their work is described in the April 15 issue of the journal Analytical Chemistry.

Typically, analytical chemists use mass spectrometry---a technique that accurately weighs molecules or fragments of molecules---to analyze proteins. In this process, proteins are introduced into the mass spectrometer and fragmented by heating until the weakest bonds break. "It's the 'shake-it-til-it-breaks' approach," Hakansson said.

Together, the masses of the various fragments provide a sort of fingerprint that reveals the genetic blueprint from which the protein was built---information that helps researchers confirm the protein's identity. This works fine as long as the protein has not been modified after it was produced. But if other chemical groups such as phosphates, sulfates or sugars have been added, the identification method breaks down.

"If sugars are attached, for instance, the weakest bonds are not the bonds that hold the protein together; they're the bonds between the sugars," Hakansson said. When those bonds break, the resulting fragments don't give accurate information about either the protein's identity or the exact type and position of sugars present.

To get around that problem, researchers have used a process called electron capture dissociation (ECD) instead of the usual "shake-it-til-it breaks" method to fragment proteins. But that method requires the presence of at least two positive charges, which can be difficult to accomplish with acidic molecules, such as proteins with sulfate or phosphate groups attached.

Hakansson's group has been exploring the use of metals such as calcium and iron to carry the necessary positive charges. In a series of recently published papers, they first showed that their method can be used to selectively cleave different bonds and then demonstrated that it can be used to identify sulfate-laden proteins and to pinpoint the location of the sulfate groups on them.

In the latest research, they extended the technique to sugars, an even more challenging task.

"Sugars are not like other biomolecules," Hakansson said. "They're linked rings with lots of branches, like trees. If you cut off a branch, you don't know which part of the tree it came from." The trick is to make breaks that cut across the ring structures, rather lopping off branches. By using metals as charge carriers, the researchers were able to do just that, yielding valuable structural information.

In a project that continues to build on this line of work, Hakansson is collaborating with U-M Health System cancer surgeon Diane Simeone to investigate sugars attached to proteins in the membranes of pancreatic cancer cells.

"The work is in very early stages, but we hope that by measuring unique sugars it may be possible to develop diagnostic tools or therapeutic agents to specifically target them," Hakansson said.

Source: University of Michigan

Related stories:

Candy-coating keeps proteins sweet
Sugar-frosting isn’t just for livening up boring bran flakes; it can also preserve important therapeutic proteins. Researchers at the National Institute of Standards and Technology have developed a fast, inexpensive and effective method for evaluating the sugars pharmaceutical companies use to stabilize protein-drugs for storage at room temperature. The group presented their findings at the 236th American Chemical Society National Meeting and Exposition.
Researchers identify an important gene for a healthy, nutritious plant
Dartmouth researchers identify an important gene for a healthy, nutritious plant. The research paper, published with colleagues from Colorado State University and the University of South Carolina, appeared in the early online edition of the Proceedings of the National Academy of Science during the week of July 21.
New Yeast Trick for Eating Favorite Food
It is well known that yeast, the humble ingredient that goes into our breads and beers, prefer to eat some sugars more than others. Glucose, their favorite food, provides more energy than any other sugar, and yeast has evolved a complex genetic network to ensure that they consume as much glucose as possible whenever it is available. UC San Diego bioengineers have recently identified a previously unknown mechanism that allows yeast to shut down the metabolism of another sugar, galactose, when they sense glucose in the environment.
Researchers identify an important gene for a healthy, nutritious plant
Dartmouth biologists have found a gene required for both efficient photosynthesis and for iron metabolism, processes necessary for producing a healthy plant and a nutritious food source. This research is part of a larger effort to learn how plants take up essential nutrients from the environment as they grow.
Plants make vaccine for treating type of cancer
Plants could act as safe, speedy factories for growing antibodies for personalized treatments against a common form of cancer, according to new findings from the Stanford University School of Medicine. The findings came in the first human tests of an injectable vaccine grown in genetically engineered plants.
Detecting flu viruses in remote areas of the world
Researchers in Ohio and New Mexico are reporting an advance in the quest for a fast, sensitive test to detect flu viruses — one that requires no refrigeration and can be used in remote areas of the world where new flu viruses often emerge. Their new method, the first to use sugar molecules rather than antibodies, is in the July 2 issue of the Journal of the American Chemical Society.
SEX4, starch and phosphorylation
Some of the new molecular mechanisms and regulatory components in starch metabolism have been identified by Dr. Samuel Zeeman and his colleagues. Dr. Zeeman, of the Institute of Plant Sciences, ETH Zurich, in Switzerland, who is the 2007 recipient of the Charles Albert Shull Award, will be presenting this work at the opening Awards Symposium of the annual meeting of the American Society of Plant Biologists in Mérida, Mexico (June 27, 2:30 PM). Mutational and structural analyses by Dr. Zeeman and his colleagues have revealed that starch degradation in Arabidopsis leaves at night differs significantly from the versions traditionally described in textbooks. Specifically, mutations at the Starch Excess 4 (SEX4), Maltose Excess 1 (MEX1) and other loci produce plants unable to metabolize starch to a usable form.
Researchers identify biofilms that cause infections
Understanding the way bacterial cells "talk" to each other could lead to more effective methods for fighting the often persistent and serious infections caused by the biofilms they form, says a Texas A&M University professor of chemical engineering who not only has deciphered their language but also discovered how to quell their conversation.

News discussion:

General Science news