German scientists have developed an automated synthesizer that can enable the use of carbohydrates in revolutionary new vaccines and drugs to battle malaria, HIV, and a bevy of other diseases.
R. Peter H. Seeberger, principal investigator for the research, developed the device at the Swiss Federal Institute of Technology in Zurich.
AdvertisementHe says that it can build intricate molecules in a few hours, instead of the months or years required with existing technology.
"Our automated synthesizer is now the fastest method to make complex carbohydrates. There are currently no competitive methods available. Today, if people working in biology run into a problem related to carbohydrates, they usually drop it because there are no tools available. They can't buy anything from a catalog. It becomes a royal pain in the neck," he says.
The researcher believes that the carbohydrate synthesizer may help kick start a revolution in the emerging fields of glycochemistry and glycobiology, named for carbohydrate sugar chains known as "glycans", in the same way as the invention of automated DNA and protein synthesizers revolutionized genetics and proteomics decades ago.
Seeberger, who reported the design of a prototype synthesizer in 2001, says that the latest version is now fully automated, much faster, and can be operated by a non-expert.
Describing it at the ACS National Meeting, the researcher said that the instrument could produce significant quantities of carbohydrate molecules that were nearly inaccessible to date.
Carbohydrates are tough molecules to build because of their complicated, branched structure, which is why in stead of building them from scratch, scientists use molecules isolated from nature, a painstaking process that could take months.
"We make things chemically that people used to isolate. The automated synthesizer puts single sugars, the building blocks of carbohydrates, together like beads on a string," explains Seeberger.
Carbohydrates play crucial roles in the immune system, especially in the body's defenses against disease-causing viruses and bacteria, most of which have unique carbohydrate markers on their surfaces.
The immune system recognizes such carbohydrates as foreign material, and creates antibodies that launch an immune response to battle the infection.
"Vaccines 'educate' the immune system to recognize a specific molecule on the surface of infectious organisms. The synthesizer allows us to make not one but many carbohydrate structures from a particular organism and test those to see if they protect against the microbe. Synthetic carbohydrates that show promising protective qualities then may become the basis for new vaccines," says Seeberger.
In a recently conducted study, Seeberger's group found a carbohydrate on the surface of the malaria parasite P. falciparum that enables the parasite to infect human red blood cells, thus solving a long-standing mystery about how infection happens.
The researchers used the carbohydrate synthesizer to develop a malaria vaccine, clinical trials for which are scheduled for 2010 in Mozambique and Tanzania.
Seeberger says that its unique "anti-disease" mechanism makes it the only vaccine of its kind.
"To my knowledge, ours is the first attempt at an anti-disease vaccine. It doesn't actually kill the malarial parasite; it blocks its toxic action. You create antibodies against the sugar structure, and these antibodies block the carbohydrate toxin from leading to inflammation and anemia, the hallmarks of malarial infection," he says.
According to him, his research group will pair the carbohydrate vaccine with a traditional, protein-based one to create a "conjugate vaccine," which is best suited to immunize the most vulnerable group of potential malaria victims, children under the age of two.
Seeberger also believes that carbohydrate-based vaccines could target some of the most serious infectious diseases, including antibiotic-resistant infections and HIV.
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