MADISON -- Probing a class of enzymes routinely used to synthesizing some of nature's most potent drugs, a team of Wisconsin scientists has found a new way to expand on nature's chemical creativity to make critical anticancer agents and antibiotics.

Writing this week (Sept. 1) in the journal Science, a team led by Jon S. Thorson, a professor of pharmaceutical sciences at the University of Wisconsin-Madison, describes the discovery of a simple process that may yield a raft of promising new agents to treat cancer and the most stubborn antibiotic-resistant infections.

"The work opens the door to a variety of new opportunities in the natural product drug arena," says Thorson.

"There are a number of antibiotics and anticancer agents this can be applied to."

In nature, plants and other organisms such as bacteria make many chemicals that can be used to treat human disease.

Such natural agents are primary sources of drugs employed to fight cancer and thwart infection.

Key chemical features of such drugs are natural sugars, molecules that frequently dictate a chemical compound's biological effects. For years, medicinal chemists have modified those natural agents to develop variants that have new or more potent disease-fighting properties. But for the most part, scientists have found it difficult to easily and routinely modify the sugar molecules that make such agents medicinally useful.

Now, Thorson and colleagues Changsheng Zhang and Byron Griffith have discovered a new and simple method to manipulate the family of enzymes nature uses to position the sugar molecules of a drug and confer a specified biological effect. The technique, according to the Science paper, has already yielded more than 70 variants of calicheamicin, an anti-tumor drug, and novel analogs of vancomycin, an antibiotic used to fight drug-resistant bacterial infections.

Prior to the new Wisconsin work, there were hints that a key class of enzymes known as glycos
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Contact: Jon S. Thorson
jsthorson@pharmacy.wisc.edu
608-262-3829
University of Wisconsin-Madison
31-Aug-2006