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Process may help scientists find new antibacterial drugs

The hunt for new antibiotic drugs, driven by emerging diseases and growing bacterial resistance to existing antibiotics, may get a little easier thanks to a new process for making compounds that contain a key bacteria-stopping structure.

The process, developed by a group of researchers led by Thomas Lectka, associate professor of chemistry at The Johns Hopkins University, will make it less expensive to create and easier to test compounds belonging to a class of drugs known as beta-lactams. Penicillin and a number of other infection-fighters are beta-lactams, but bacterial resistance has reduced the usefulness of an increasing number of these drugs.

Lectka, who describes the new process in a report in the online version of The Journal of the American Chemical Society [scroll down to Aug. 2], hopes his work will facilitate the creation of new beta-lactam drugs.

"Beta-lactams have been critical tools for fighting the spread of bacterial infections in the past, and they could be so again," Lectka says. "It's also important to note that while beta-lactams have traditionally been used as antibiotics, they have recently found use in treating patients with conditions ranging from arthritis to HIV."

Beta-lactams's distinguishing characteristic is a high-energy ring of three carbon atoms and one nitrogen atom known as a beta-lactam ring.

"This ring wants to pop open," Lectka explains, "but it doesn't typically do that until a bacterial enzyme comes along and mistakes it for a substrate, a material chemically modified by the enzyme. When the enzyme uses the beta-lactam, the ring snaps open, disabling the enzyme and effectively killing the bacteria."

After decades of overuse of penicillin and other popular antibiotics, though, many bacteria have developed enzymes that disable the beta-lactam rings first. Those enzymes are
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Contact: Michael Purdy
mcp@jhu.edu
410-516-7160
Johns Hopkins University
27-Aug-2000


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