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

15 Scopus citations

Abstract

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 (US)
Pages (from-to)216-220
Number of pages5
JournalACS Medicinal Chemistry Letters
Volume6
Issue number2
DOIs
StatePublished - Feb 12 2015
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

Fingerprint

Dive into the research topics of 'Improved synthesis of biotinol-5′-AMP: Implications for antibacterial discovery'. Together they form a unique fingerprint.

Cite this