Antibacterial Discovery via Phenotypic DNA-Encoded Library Screening
| Autor: | Brian M. Paegel, Patrick R. Fitzgerald, Wesley G. Cochrane |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Apoptosis
Bacillus subtilis Computational biology medicine.disease_cause Biochemistry chemistry.chemical_compound Structure-Activity Relationship Scalable design Ciprofloxacin Drug Discovery medicine Escherichia coli Cytotoxicity Piperazine Gene Library biology Molecular Structure General Medicine DNA biology.organism_classification Phenotype Anti-Bacterial Agents High-Throughput Screening Assays Multiple drug resistance chemistry Molecular Medicine |
| Zdroj: | ACS chemical biology. 16(12) |
| ISSN: | 1554-8937 |
| Popis: | The global rise of multidrug resistant infections poses an imminent, existential threat. Numerous pipelines have failed to convert biochemically active molecules into bona fide antibacterials, owing to a lack of chemical material with antibacterial-like physical properties in high-throughput screening compound libraries. Here, we demonstrate scalable design and synthesis of an antibacterial-like solid-phase DNA-encoded library (DEL, 7488 members) and facile hit deconvolution from whole-cell Escherichia coli and Bacillus subtilis cytotoxicity screens. The screen output identified two low-micromolar inhibitors of B. subtilis growth and recapitulated known structure-activity relationships of the fluoroquinolone antibacterial class. This phenotypic DEL screening strategy is also potentially applicable to adherent cells and will broadly enable the discovery and optimization of cell-active molecules. |
| Databáze: | OpenAIRE |
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