Improved synthesis of biotinol-5'-AMP: implications for antibacterial discovery
Date
2015
Authors
Tieu, W.
Polyak, S.
Paparella, A.
Yap, M.
Soares Da Costa, T.
Ng, B.
Wang, G.
Lumb, R.
Bell, J.
Turnidge, J.
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Journal article
Citation
ACS Medicinal Chemistry Letters, 2015; 6(2):216-220
Statement of Responsibility
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, and Andrew D. Abell
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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.
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Copyright © 2014 American Chemical Society