Improved synthesis of biotinol-5′-AMP: Implications for antibacterial discovery

William Tieu, Steven W. Polyak, Ashleigh S. Paparella, Min Y. Yap, Tatiana P. Soares Da Costa, Belinda Ng, Geqing Wang, Richard Lumb, Jan M. Bell, John D. Turnidge, Matthew C.J. Wilce, Grant W. Booker, Andrew D. Abell

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)


An improved synthesis of biotinol-5′-AMP, an acyl-AMP mimic of the natural reaction intermediate of biotin protein ligase (BPL), is reported. This compound was shown to be a pan inhibitor of BPLs from a series of clinically important bacteria, particularly Staphylococcus aureus and Mycobacterium tuberculosis, and kinetic analysis revealed it to be competitive against the substrate biotin. Biotinol-5′-AMP also exhibits antibacterial activity against a panel of clinical isolates of S. aureus and M. tuberculosis with MIC values of 1-8 and 0.5-2.5 μg/mL, respectively, while being devoid of cytotoxicity to human HepG2 cells.

Original languageEnglish
Pages (from-to)216-220
Number of pages5
JournalACS Medicinal Chemistry Letters
Issue number2
Publication statusPublished or Issued - 12 Feb 2015
Externally publishedYes


  • Antibiotics
  • biotin protein ligase
  • chemical synthesis
  • drug design
  • enzyme inhibitors

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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