A sweet step toward new cancer therapies

Mar 31, 2007

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

Explore further: Chemical biologists find new halogenation enzyme

add to favorites email to friend print save as pdf

Related Stories

History books spark latest Texas classroom battle

20 minutes ago

As Texas mulls new history textbooks for its 5-plus million public school students, some academics are decrying lessons they say exaggerate the influence of Christian values on America's Founding Fathers.

Flatow, 'Science Friday' settle claims over grant

36 minutes ago

Federal prosecutors say radio host Ira Flatow and his "Science Friday" show that airs on many National Public Radio stations have settled civil claims that they misused money from a nearly $1 million federal ...

Tokyo Game Show: On the hunt for the next Minecraft

39 minutes ago

The staggering $2.5 billion that Microsoft has just shelled out for Minecraft and its quirky graphics will be foremost in developers' minds at the Tokyo Game Show this week, where simple yet immersive games ...

Recommended for you

Chemical biologists find new halogenation enzyme

23 hours ago

Molecules containing carbon-halogen bonds are produced naturally across all kingdoms of life and constitute a large family of natural products with a broad range of biological activities. The presence of halogen substituents ...

Protein secrets of Ebola virus

Sep 15, 2014

The current Ebola virus outbreak in West Africa, which has claimed more than 2000 lives, has highlighted the need for a deeper understanding of the molecular biology of the virus that could be critical in ...

Protein courtship revealed through chemist's lens

Sep 15, 2014

Staying clear of diseases requires that the proteins in our cells cooperate with one another. But, it has been a well-guarded secret how tens of thousands of different proteins find the correct dancing partners ...

User comments : 0