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UW-Madison scientists zero in on drugs' sweet spots

Employing a simple new technique to manipulate the sugars that power many front-line drugs, a team of Wisconsin scientists has enhanced the antic-cancer properties of a digitalis, a drug commonly used to treat heart disease.

Reporting the work in the Aug. 8 edition of the Proceedings of the National Academy of Sciences, a team led by University of Wisconsin-Madison professor of pharmaceutical sciences Jon S. Thorson, describes a series of experiments that boosted the cell-killing potency and tumor specificity of the drug, derived from the foxglove plant and used to stimulate the heart. The drug is suspected to have anti-cancer properties, but its use to treat cancer has been little explored.

The new work is important because it provides scientists and drug companies with a quick and easy way to manipulate the sugars found in chemicals produced in nature. Such chemicals -- often found in microbes, plants and marine organisms -- are the bedrock agents upon which many leading drugs are built. The ways sugar groups are organized on a molecule often dictate the agent's biological effects.

"In the past, to alter the sugars attached to these drugs was very difficult," explains Thorson, of the UW-Madison Pharmacy School's Laboratory for Biosynthetic Chemistry. "These are very complex molecules."

The new technique replaces enzymes, biological catalysts, with a robust chemical method, allowing researchers to easily manipulate and exchange the sugars found in natural agents.

Critically, the method allows medicinal chemists to investigate the biological effects of the many forms of sugars or carbohydrates found in nature. "There are many different variations of sugars -- they're all over the place in nature -- and they are very important. This method allows us to rapidly scan the roles of these sugars in complex natural products."

The simplification of the process to manipulate natural sugars could help make natural products more a
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Source:University of Wisconsin-Madison


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