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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 ?g/mL, respectively, while being devoid of cytotoxicity to human HepG2 cells.

SUBMITTER: Tieu W

PROVIDER: S-EPMC4329585 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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Improved Synthesis of Biotinol-5'-AMP: Implications for Antibacterial Discovery.

Tieu William W Polyak Steven W SW Paparella Ashleigh S AS Yap Min Y MY Soares da Costa Tatiana P TP Ng Belinda B Wang Geqing G Lumb Richard R Bell Jan M JM Turnidge John D JD Wilce Matthew C J MC Booker Grant W GW Abell Andrew D AD

ACS medicinal chemistry letters 20141211 2

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 ...[more]

PMID: 25699152

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