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Enzyme Inhibitor May Be Potential Antibiotic

Kate Traynor

University of Michigan School of Pharmacy researchers have identified an easy-to-synthesize compound that has the potential to become a potent antibiotic against gram-negative bacteria.

The compound, dubbed "PD 404182," blocks the action of an enzyme required to maintain the cell wall of gram-negative bacteria. At present, no antibiotics that target the enzyme, known as KDO 8-P synthase, are commercially available.

According to the study, which appeared in the Sept. 27 Journal of the American Chemical Society, PD 404182 was 10,000 times as potent in laboratory tests as other experimental compounds that inhibit the enzyme. However, inhibition was much weaker when PD 404182 was tested in live bacteria.

The researchers reported that they have begun structural studies of PD 404182 in the hope of producing a version that works effectively against live gram-negative bacteria.