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

doi:10.1021/ml500475n

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 journal › Article › peer-review

16 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 language	English
Pages (from-to)	216-220
Number of pages	5
Journal	ACS Medicinal Chemistry Letters
Volume	6
Issue number	2
DOIs	https://doi.org/10.1021/ml500475n
Publication status	Published or Issued - 12 Feb 2015
Externally published	Yes

Keywords

Antibiotics
biotin protein ligase
chemical synthesis
drug design
enzyme inhibitors

ASJC Scopus subject areas

Biochemistry
Drug Discovery
Organic Chemistry

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10.1021/ml500475n

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title = "Improved synthesis of biotinol-5′-AMP: Implications for antibacterial discovery",

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.",

keywords = "Antibiotics, biotin protein ligase, chemical synthesis, drug design, enzyme inhibitors",

author = "William Tieu and Polyak, {Steven W.} and Paparella, {Ashleigh S.} and Yap, {Min Y.} and {Soares Da Costa}, {Tatiana P.} and Belinda Ng and Geqing Wang and Richard Lumb and Bell, {Jan M.} and Turnidge, {John D.} and Wilce, {Matthew C.J.} and Booker, {Grant W.} and Abell, {Andrew D.}",

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doi = "10.1021/ml500475n",

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journal = "ACS Medicinal Chemistry Letters",

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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 P.

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 - Abell, Andrew D.

PY - 2015/2/12

Y1 - 2015/2/12

N2 - 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.

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.

KW - Antibiotics

KW - biotin protein ligase

KW - chemical synthesis

KW - drug design

KW - enzyme inhibitors

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SN - 1948-5875

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ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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