title: An azido-oxazolidinone antibiotic for live bacterial cell imaging and generation of antibiotic variants.
abstract: An azide-functionalised analogue of the oxazolidinone antibiotic linezolid was synthesised and shown to retain antimicrobial activity. Using facile 'click' chemistry, this versatile intermediate can be further functionalised to explore antimicrobial structure-activity relationships or conjugated to fluorophores to generate fluorescent probes. Such probes can report bacteria and their location in a sample in real time. Modelling of the structures bound to the cognate 50S ribosome target demonstrates binding to the same site as linezolid is possible. The fluorescent probes were successfully used to image Gram-positive bacteria using confocal microscopy.
authors.affiliation: Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.
authors.forename: Wanida
authors.initials: W
authors.lastname: Phetsang
authors.affiliation: Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia. Electronic address: m.blaskovich@uq.edu.au.
authors.forename: Mark A T
authors.initials: MA
authors.lastname: Blaskovich
authors.affiliation: Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Butler
authors.affiliation: Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.
authors.forename: Johnny X
authors.initials: JX
authors.lastname: Huang
authors.affiliation: Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.
authors.forename: Johannes
authors.initials: J
authors.lastname: Zuegg
authors.affiliation: Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.
authors.forename: Sreeman K
authors.initials: SK
authors.lastname: Mamidyala
authors.affiliation: Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.
authors.forename: Soumya
authors.initials: S
authors.lastname: Ramu
authors.affiliation: Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Kavanagh
authors.affiliation: Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia. Electronic address: m.cooper@uq.edu.au.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Cooper
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001386:Azides / Q000737:chemistry / Q000494:pharmacology*; D057930:Click Chemistry; D015195:Drug Design; D005456:Fluorescent Dyes / Q000032:analysis* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006094:Gram-Positive Bacteria / Q000166:cytology* / Q000187:drug effects* / Q000302:isolation & purification; D008826:Microbial Sensitivity Tests; D018613:Microscopy, Confocal; D008958:Models, Molecular; D015394:Molecular Structure; D023303:Oxazolidinones / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D001386:Azides; D005456:Fluorescent Dyes; D023303:Oxazolidinones
keywords: Antibiotics; Bacteria; Click chemistry; Fluorescent probes; Linezolid