Carbohydrates are not just a much-maligned food group, they are molecules vital to all living systems, taking part in everything from immune response to brain function. Made up of long, often highly branched chains of specific sugar molecules, carbohydrates are notoriously difficult to study, so they are far less well understood than other biological molecules, like proteins or DNA.
Now, chemists funded by the National Institute of General Medical Sciences (NIGMS) have discovered a way to control the cellular machinery that puts finishing touches on many carbohydrate molecules. The work promises to reveal insights about the diverse roles played by carbohydrates and may pave the way for new therapies to heal wounds, reduce chronic inflammation, regenerate damaged nerves, and treat cancer.
Carbohydrates get attached to proteins to form glycoproteins in a cellular organelle called the Golgi complex. Enzymes in the Golgi also add chemical groups called sulfates to strategic locations on specific carbohydrates. Sulfates are important for many of the reactions carried out by glycoproteins.
The scientists, led by Carolyn Bertozzi, Ph.D., of the University of California, Berkeley, created a chemical switch to turn the addition of sulfate on and off at will, providing a way to study and possibly control a wide range of cellular processes. The new technique builds on earlier work in which Bertozzi’s group developed a way to harness other Golgi enzymes to make customized carbohydrates on proteins.
“This is an exciting technique that promises to reveal new insights about how cells control a chemical process essential to life,” said Pamela Marino, Ph.D., an expert in carbohydrate chemistry at NIGMS. “While Bertozzi’s work is still at a very basic level, we can begin to see how it may lead to practical benefits for human health.”
A number of other NIGMS grantees are similarly using small chemicals to control biological processes. This powerful approach allows scientists to precisely perturb a cellular process at a specific time and place, or only under certain conditions. Watching the effect of such an intervention helps the scientists better understand how biological molecules and environmental factors work together in healthy or diseased cells. This deepened understanding may undergird new ways to treat or diagnose diseases in the future.
The research appears in the November 30 issue of the Proceedings of the National Academy of Sciences.
NIGMS supports basic biomedical research that lays the foundation for advances in disease diagnosis, treatment, and prevention. It is part of the National Institutes of Health, U.S. Department of Health and Human Services.
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Reference: de Graffenried CL, Laughlin ST, Kohler JJ, Bertozzi CR. A small-molecule switch for Golgi sulfotransferases. PNAS 101: 16715-16720, 2004
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