Polyphosphate-containing bisubstrate analogues as inhibitors of a bacterial cell wall thymidylyltransferase

Deborah A. Smithen; Stephanie M. Forget; Nicole E. McCormick; Raymond T. Syvitski; David L. Jakeman

doi:10.1039/C4OB02583K

Polyphosphate-containing bisubstrate analogues as inhibitors of a bacterial cell wall thymidylyltransferase

Deborah A. Smithen,^a Stephanie M. Forget,^a Nicole E. McCormick,^b Raymond T. Syvitski^a and David L. Jakeman*^a^b

Author affiliations

* Corresponding authors

^a Department of Chemistry, Dalhousie University, 6274 Coburg Rd., PO Box 15, 000, Halifax, Canada
E-mail: david.jakeman@dal.ca

^b College of Pharmacy, Dalhousie University, 5968 College St., PO Box15, 000, Halifax, Canada

Abstract

A series of polyphosphate containing sugar nucleotide analogues were synthesized and evaluated as bisubstrate inhibitors of α-D-glucose 1-phosphate thymidylyltransferase Cps2L, the first enzyme in Streptococcus pneumoniaeL-rhamnose biosynthesis, and a novel antibacterial target. WaterLOGSY NMR spectroscopy demonstrated binding of bisubstrate analogues to Cps2L and a spectrophotometric coupled assay was used to determine apparent K_i values.

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Publication details

The article was received on 10 Dec 2014, accepted on 27 Jan 2015 and first published on 27 Jan 2015

Article type: Paper

DOI: 10.1039/C4OB02583K

Author version available: Download Author version (PDF)

Citation: Org. Biomol. Chem., 2015,13, 3347-3350

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Polyphosphate-containing bisubstrate analogues as inhibitors of a bacterial cell wall thymidylyltransferase

D. A. Smithen, S. M. Forget, N. E. McCormick, R. T. Syvitski and D. L. Jakeman, Org. Biomol. Chem., 2015, 13, 3347
DOI: 10.1039/C4OB02583K
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Organic & Biomolecular Chemistry

Polyphosphate-containing bisubstrate analogues as inhibitors of a bacterial cell wall thymidylyltransferase

Abstract

Supplementary files

Publication details

Polyphosphate-containing bisubstrate analogues as inhibitors of a bacterial cell wall thymidylyltransferase

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