Design, synthesis, and evaluation of transition-state analogs as inhibitors of the bacterial quorum sensing autoinducer synthase CepI
| Autor: | Julia G. Stockwell, Sterling R. Payne, Julian S. Kellner-Rogers, Nora R. Vail, Scott M. Ulrich, Erin Leigh Higgins, Alec C. Esposito, Alexandra M. Estanislau |
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| Rok vydání: | 2021 |
| Předmět: |
Clinical Biochemistry
Homoserine Pharmaceutical Science Virulence 01 natural sciences Biochemistry Article Ligases Lactones Structure-Activity Relationship chemistry.chemical_compound Transition state analog Drug Discovery Secretion Enzyme Inhibitors Molecular Biology Dose-Response Relationship Drug Molecular Structure biology ATP synthase 010405 organic chemistry Organic Chemistry Quorum Sensing biochemical phenomena metabolism and nutrition biology.organism_classification 0104 chemical sciences 010404 medicinal & biomolecular chemistry Quorum sensing chemistry Drug Design biology.protein Molecular Medicine Autoinducer Bacteria |
| Zdroj: | Bioorg Med Chem Lett |
| ISSN: | 0960-894X |
| Popis: | Quorum sensing is a bacterial signaling system that involves the synthesis, secretion and detection of signal molecules called autoinducers. The main autoinducer in Gram-negative bacteria are acylated homoserine lactones, produced by the LuxI family of autoinducer synthases and detected by the LuxR family of autoinducer receptors. Quorum sensing allows for changes in gene expression and bacterial behaviors in a coordinated, cell density dependent manner. Quorum sensing controls the expression of virulence factors in some human pathogens, making quorum sensing an antibacterial drug target. Here we describe the design and synthesis of transition-state analogs of the autoinducer synthase enzymatic reaction and the evaluation of these compounds as inhibitors of the synthase CepI. One such compound potently inhibits CepI and constitutes a new type of inhibitor against this underdeveloped antibacterial target. |
| Databáze: | OpenAIRE |
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