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

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

Research output: Contribution to journalArticle

10 Citations (Scopus)

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
Pages (from-to)216-220
Number of pages5
JournalACS Medicinal Chemistry Letters
Volume6
Issue number2
Early online date2014
DOIs
Publication statusPublished - Feb 2015

    Fingerprint

Cite this

Tieu, W., Polyak, S. W., Paparella, A. S., Yap, M. Y., Soares da Costa, T., Ng, B., Wang, G., Lumb, R., Bell, J. M., Turnidge, J. D., Wilce, M. C. J., Booker, G. W., & Abel, A. D. (2015). Improved synthesis of biotinol-5'-AMP: Implications for antibacterial discovery. ACS Medicinal Chemistry Letters, 6(2), 216-220. https://doi.org/10.1021/ml500475n