Heterocyclic acyl-phosphate bioisostere-based inhibitors of Staphylococcus aureus biotin protein ligase

William Tieu, Angie M. Jarrad, Ashleigh S. Paparella, Kelly A. Keeling, Tatiana P. Soares Da Costa, John C. Wallace, Grant W. Booker, Steven W. Polyak, Andrew D. Abell

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11 Citations (Scopus)

Abstract

Inhibitors of Staphylococcus aureus biotin protein ligase (SaBPL) are generated by replacing the acyl phosphate group of biotinyl-5′-AMP with either a 1,2,3-triazole (see 5/10a/10b) or a 1,2,4-oxadiazole (see 7) bioisostere. Importantly, the inhibitors are inactive against the human BPL. The nature of the 5-substituent in the component benzoxazolone of the optimum 1,2,3-triazole series is critical to activity, where this group binds in the ATP binding pocket of the enzyme.

LanguageEnglish
Pages4689-4693
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume24
Issue number19
DOIs
Publication statusPublished - 1 Oct 2014

Keywords

  • Antibiotics
  • Bioisosteres
  • Drug design
  • Inhibitors
  • Ligases

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Tieu, W., Jarrad, A. M., Paparella, A. S., Keeling, K. A., Soares Da Costa, T. P., Wallace, J. C., ... Abell, A. D. (2014). Heterocyclic acyl-phosphate bioisostere-based inhibitors of Staphylococcus aureus biotin protein ligase. Bioorganic and Medicinal Chemistry Letters, 24(19), 4689-4693. https://doi.org/10.1016/j.bmcl.2014.08.030