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Figure 3. WT S. aureus macromolecular labeling with analogue 1b.
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synthetase component to the mechanism of action.
In conclusion, a novel structural class of spirocyclic
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against E. faecalis and S. aureus PheRSs with high selec-
tivity over the human enzyme has been discovered. These
compounds also exhibit E. coli PheRS inhibitory activity.
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Acknowledgements
The authors would like to thank the Biological and Ana-
lytical staff at Cubist for enzyme assay data and spectra,
Professor J. A. Golen at University of Masechusetts at
Dartmouth for the crystal X-ray structure, and the staff at
Bristol-Myers for 1H NMR NOE experiments.
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References and notes
1. Fernandez-Lopez, S.; Kim, H.; Choi, E. C.; Delgado, M.;
Granja, J. R.; Khasanov, A.; Kraehenbuehl, K.; Long,