ArticleThe Journal of biological chemistry2012
Selective inhibition of biotin protein ligase from Staphylococcus aureus.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 67 citations in OpenAlex.
- Catalyst-Free Biotin Conjugation Onto Poly(Styrene-co-Butadiene) Mediated by an Orthogonal Agent Comprising Nitrile N-Oxide and Blocked Isocyanate.Macromolecular rapid communications · 2026Article
- Click Reactions in Kinetic Target-Guided Synthesis: Progress in the Discovery of Inhibitors for Biological Targets.Methods and protocols · 2026Review
- Hydrogen-Deuterium Exchange Defines Ligand-Induced Conformational Changes to the Class III Biotin Protein Ligase from Saccharomyces cerevisiae.Chembiochem : a European journal of chemical biology · 2025Article
- Pathogenic bacteria enriched in the oral microbiota might be associated with recurrent pulmonary infections in elderly individuals.Aging clinical and experimental research · 2025Article
- New Potent Sulfonamide-Based Inhibitors ofACS medicinal chemistry letters · 2024Article
- A toolbox for genetic manipulation in intestinalSynthetic and systems biotechnology · 2024Article
- Repurposed inhibitor of bacterial dihydrodipicolinate reductase exhibits effective herbicidal activity.Communications biology · 2023Article
- Structural Study of Potent Triazole-Based Inhibitors ofACS medicinal chemistry letters · 2023Article
- Emergence of allostery through reorganization of protein residue network architecture.The Journal of chemical physics · 2023Article
- Synthesis, antimicrobial activity and molecular docking studies of spiroquinoline-indoline-dione and spiropyrazolo-indoline-dione derivatives.Scientific reports · 2023Article
- Identification of Putative Vaccine and Drug Targets against the Methicillin-ResistantMolecules (Basel, Switzerland) · 2022Article
- Functional dissection and modulation of the BirA protein for improved autotrophic growth of gas-fermenting Clostridium ljungdahlii.Microbial biotechnology · 2021Article
- Article
- Advanced Resistance Studies Identify Two Discrete Mechanisms inAntibiotics (Basel, Switzerland) · 2020Article
- The Biotin Biosynthetic Pathway in Mycobacterium tuberculosis is a Validated Target for the Development of Antibacterial Agents.Current medicinal chemistry · 2020Review
- Biotin-Labelled Clavulanic Acid to Identify Proteins Target for Haptenation in Serum: Implications in Allergy Studies.Frontiers in pharmacology · 2020Article
- Structure-Based Design, Synthesis, and Biological Evaluation of Non-Acyl Sulfamate Inhibitors of the Adenylate-Forming Enzyme MenE.Biochemistry · 2019Article
- Native mass spectrometry identifies an alternative DNA-binding pathway for BirA from Staphylococcus aureus.Scientific reports · 2019Article
- Antitubercular activity of 1,2,3-triazolyl fatty acid derivatives.European journal of medicinal chemistry · 2017Article
- New Series of BPL Inhibitors To Probe the Ribose-Binding Pocket ofACS medicinal chemistry letters · 2016Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
There is a well documented need to replenish the antibiotic pipeline with new agents to combat the rise of drug resistant bacteria. One strategy to combat resistance is to discover new chemical classes immune to current resistance mechanisms that inhibit essential metabolic enzymes. Many of the obvious drug targets that have no homologous isozyme in the human host have now been investigated. Bacterial drug targets that have a closely related human homologue represent a new frontier in antibiotic discovery. However, to avoid potential toxicity to the host, these inhibitors must have very high selectivity for the bacterial enzyme over the human homolog. We have demonstrated that the essential enzyme biotin protein ligase (BPL) from the clinically important pathogen Staphylococcus aureus could be selectively inhibited. Linking biotin to adenosine via a 1,2,3 triazole yielded the first BPL inhibitor selective for S. aureus BPL over the human equivalent. The synthesis of new biotin 1,2,3-triazole analogues using click chemistry yielded our most potent structure (K(i) 90 nM) with a >1100-fold selectivity for the S. aureus BPL over the human homologue. X-ray crystallography confirmed the mechanism of inhibitor binding. Importantly, the inhibitor showed cytotoxicity against S. aureus but not cultured mammalian cells. The biotin 1,2,3-triazole provides a novel pharmacophore for future medicinal chemistry programs to develop this new antibiotic class.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.