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Science 16 April 1999:
Vol. 284. no. 5413, pp. 507 - 511
DOI: 10.1126/science.284.5413.507
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Reports

Vancomycin Derivatives That Inhibit Peptidoglycan Biosynthesis Without Binding D-Ala-D-Ala

Min Ge, 1 Zhong Chen, 1 H. Russell Onishi , Joyce Kohler, 2 Lynn L. Silver, 2 Robert Kerns, 1 Seketsu Fukuzawa, 1 Christopher Thompson, 1 Daniel Kahne 1*

Vancomycin is an important drug for the treatment of Gram-positive bacterial infections. Resistance to vancomycin has begun to appear, posing a serious public health threat. Vancomycin analogs containing modified carbohydrates are very active against resistant microorganisms. Results presented here show that these carbohydrate derivatives operate by a different mechanism than vancomycin; moreover, peptide binding is not required for activity. It is proposed that carbohydrate-modified vancomycin compounds are effective against resistant bacteria because they interact directly with bacterial proteins involved in the transglycosylation step of cell wall biosynthesis. These results suggest new strategies for designing glycopeptide antibiotics that overcome bacterial resistance.

1 Department of Chemistry, Princeton University Princeton, NJ 08544, USA.
2 Infectious Diseases, Merck Research Laboratories, Rahway, NJ 07065, USA.
*   To whom correspondence should be addressed. E-mail: dkahne{at}princeton.edu

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