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

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Adenosine Monophosphate
Biotin
Mycobacterium tuberculosis
Staphylococcus aureus
Reaction intermediates
Hep G2 Cells
Cytotoxicity
Ligases
Bacteria
Kinetics
Substrates
Proteins

Cite this

Tieu, W., Polyak, S. W., Paparella, A. S., Yap, M. Y., Soares da Costa, T., Ng, B., ... 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
Tieu, William ; Polyak, Steven W. ; Paparella, Ashleigh S. ; Yap, Min Y. ; Soares da Costa, Tatiana ; Ng, Belinda ; Wang, Geqing ; Lumb, Richard ; Bell, Jan M. ; Turnidge, John D. ; Wilce, Matthew C. J. ; Booker, Grant W. ; Abel, Andrew D. / Improved synthesis of biotinol-5'-AMP : Implications for antibacterial discovery. In: ACS Medicinal Chemistry Letters. 2015 ; Vol. 6, No. 2. pp. 216-220.
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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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Tieu, W, Polyak, SW, Paparella, AS, Yap, MY, Soares da Costa, T, Ng, B, Wang, G, Lumb, R, Bell, JM, Turnidge, JD, Wilce, MCJ, Booker, GW & Abel, AD 2015, 'Improved synthesis of biotinol-5'-AMP: Implications for antibacterial discovery', ACS Medicinal Chemistry Letters, vol. 6, no. 2, pp. 216-220. https://doi.org/10.1021/ml500475n

Improved synthesis of biotinol-5'-AMP : Implications for antibacterial discovery. / Tieu, William; Polyak, Steven W.; Paparella, Ashleigh S.; Yap, Min Y.; Soares da Costa, Tatiana; Ng, Belinda; Wang, Geqing; Lumb, Richard; Bell, Jan M.; Turnidge, John D.; Wilce, Matthew C. J.; Booker, Grant W.; Abel, Andrew D.

In: ACS Medicinal Chemistry Letters, Vol. 6, No. 2, 02.2015, p. 216-220.

Research output: Contribution to journalArticle

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T1 - Improved synthesis of biotinol-5'-AMP

T2 - Implications for antibacterial discovery

AU - Tieu, William

AU - Polyak, Steven W.

AU - Paparella, Ashleigh S.

AU - Yap, Min Y.

AU - Soares da Costa, Tatiana

AU - Ng, Belinda

AU - Wang, Geqing

AU - Lumb, Richard

AU - Bell, Jan M.

AU - Turnidge, John D.

AU - Wilce, Matthew C. J.

AU - Booker, Grant W.

AU - Abel, Andrew D.

N1 - Includes bibliographical references.

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AB - 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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KW - Biotin protein ligase

KW - Chemical synthesis

KW - Drug design

KW - Enzyme inhibitors

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Tieu W, Polyak SW, Paparella AS, Yap MY, Soares da Costa T, Ng B et al. Improved synthesis of biotinol-5'-AMP: Implications for antibacterial discovery. ACS Medicinal Chemistry Letters. 2015 Feb;6(2):216-220. https://doi.org/10.1021/ml500475n