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.
authors.affiliation: School of Chemistry and Physics, University of Adelaide , Adelaide, South Australia 5005, Australia ; Centre for Molecular Pathology, The University of Adelaide , Adelaide, South Australia 5005, Australia.
authors.forename: William
authors.initials: W
authors.lastname: Tieu
authors.affiliation: School of Molecular and Biomedical Science, University of Adelaide , Adelaide, South Australia 5005, Australia ; Centre for Molecular Pathology, The University of Adelaide , Adelaide, South Australia 5005, Australia.
authors.forename: Steven W
authors.initials: SW
authors.lastname: Polyak
authors.affiliation: School of Molecular and Biomedical Science, University of Adelaide , Adelaide, South Australia 5005, Australia.
authors.forename: Ashleigh S
authors.initials: AS
authors.lastname: Paparella
authors.affiliation: School of Biomedical Science, Monash University , Victoria 3800, Australia.
authors.forename: Min Y
authors.initials: MY
authors.lastname: Yap
authors.affiliation: School of Molecular and Biomedical Science, University of Adelaide , Adelaide, South Australia 5005, Australia.
authors.forename: Tatiana P
authors.initials: TP
authors.lastname: Soares da Costa
authors.affiliation: School of Molecular and Biomedical Science, University of Adelaide , Adelaide, South Australia 5005, Australia.
authors.forename: Belinda
authors.initials: B
authors.lastname: Ng
authors.affiliation: School of Molecular and Biomedical Science, University of Adelaide , Adelaide, South Australia 5005, Australia.
authors.forename: Geqing
authors.initials: G
authors.lastname: Wang
authors.affiliation: Microbiology and Infectious Diseases Directorate, SA Pathology, Women's and Children's Hospital , Adelaide, South Australia 5006, Australia.
authors.forename: Richard
authors.initials: R
authors.lastname: Lumb
authors.affiliation: Microbiology and Infectious Diseases Directorate, SA Pathology, Women's and Children's Hospital , Adelaide, South Australia 5006, Australia.
authors.forename: Jan M
authors.initials: JM
authors.lastname: Bell
authors.affiliation: School of Molecular and Biomedical Science, University of Adelaide , Adelaide, South Australia 5005, Australia ; Microbiology and Infectious Diseases Directorate, SA Pathology, Women's and Children's Hospital , Adelaide, South Australia 5006, Australia.
authors.forename: John D
authors.initials: JD
authors.lastname: Turnidge
authors.affiliation: School of Biomedical Science, Monash University , Victoria 3800, Australia.
authors.forename: Matthew C J
authors.initials: MC
authors.lastname: Wilce
authors.affiliation: School of Molecular and Biomedical Science, University of Adelaide , Adelaide, South Australia 5005, Australia ; Centre for Molecular Pathology, The University of Adelaide , Adelaide, South Australia 5005, Australia.
authors.forename: Grant W
authors.initials: GW
authors.lastname: Booker
authors.affiliation: School of Chemistry and Physics, University of Adelaide , Adelaide, South Australia 5005, Australia ; Centre for Molecular Pathology, The University of Adelaide , Adelaide, South Australia 5005, Australia.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Abell
keywords: Antibiotics; biotin protein ligase; chemical synthesis; drug design; enzyme inhibitors