Improved synthesis of biotinol-5'-AMP: implications for antibacterial discovery

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

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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 mug/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 - 2015

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