title: Heterocyclic acyl-phosphate bioisostere-based inhibitors of Staphylococcus aureus biotin protein ligase.
abstract: Inhibitors of Staphylococcus aureus biotin protein ligase (SaBPL) are generated by replacing the acyl phosphate group of biotinyl-5'-AMP with either a 1,2,3-triazole (see 5/10a/10b) or a 1,2,4-oxadiazole (see 7) bioisostere. Importantly, the inhibitors are inactive against the human BPL. The nature of the 5-substituent in the component benzoxazolone of the optimum 1,2,3-triazole series is critical to activity, where this group binds in the ATP binding pocket of the enzyme.
authors.affiliation: School of Chemistry and Physics, University of Adelaide, Adelaide, South Australia 5005, Australia. Electronic address: william.tieu@adelaide.edu.au.
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.
authors.forename: Angie M
authors.initials: AM
authors.lastname: Jarrad
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 Chemistry and Physics, University of Adelaide, Adelaide, South Australia 5005, Australia.
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Keeling
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: John C
authors.initials: JC
authors.lastname: Wallace
authors.affiliation: School of Molecular and Biomedical Science, University of Adelaide, Adelaide, South Australia 5005, Australia.
authors.forename: Grant W
authors.initials: GW
authors.lastname: Booker
authors.affiliation: School of Molecular and Biomedical Science, University of Adelaide, Adelaide, South Australia 5005, Australia.
authors.forename: Steven W
authors.initials: SW
authors.lastname: Polyak
authors.affiliation: School of Chemistry and Physics, University of Adelaide, Adelaide, South Australia 5005, Australia. Electronic address: andrew.abell@adelaide.edu.au.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Abell
mesh_terms: D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001710:Biotin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008025:Ligases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D010755:Organophosphates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000201:enzymology
chemical_list: D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D006571:Heterocyclic Compounds; D010755:Organophosphates; D001710:Biotin; D008025:Ligases
keywords: Antibiotics; Bioisosteres; Drug design; Inhibitors; Ligases