Rational Design, Synthesis, and Preliminary Structure-Activity Relationships of α-Substituted-2-Phenylcyclopropane Carboxylic Acids as Inhibitors of Salmonella typhimurium O-Acetylserine Sulfhydrylase
| العنوان: | Rational Design, Synthesis, and Preliminary Structure-Activity Relationships of α-Substituted-2-Phenylcyclopropane Carboxylic Acids as Inhibitors of Salmonella typhimurium O-Acetylserine Sulfhydrylase |
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| المؤلفون: | Thelma A. Pertinhez, Roberto Benoni, Andrea Mozzarelli, Randy Wouters, Barbara Campanini, Giannamaria Annunziato, Claudia Beato, Stefano Bettati, Marco Pieroni, Gabriele Costantino |
| المصدر: | Journal of medicinal chemistry 59 (2016): 2567–2578. doi:10.1021/acs.jmedchem.5b01775 info:cnr-pdr/source/autori:Pieroni M, Annunziato G, Beato C, Wouters R, Benoni R, Campanini B, Pertinhez TA, Bettati S, Mozzarelli A, Costantino G/titolo:Rational Design, Synthesis, and Preliminary Structure-Activity Relationships of alpha-Substituted-2-Phenylcyclopropane Carboxylic Acids as Inhibitors of Salmonella typhimurium O-Acetylserine Sulfhydrylase/doi:10.1021%2Facs.jmedchem.5b01775/rivista:Journal of medicinal chemistry/anno:2016/pagina_da:2567/pagina_a:2578/intervallo_pagine:2567–2578/volume:59 |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 0301 basic medicine, Cyclopropanes, Models, Molecular, Salmonella typhimurium, Magnetic Resonance Spectroscopy, Stereochemistry, Carboxylic Acids, Swarming motility, Microbial Sensitivity Tests, Cysteine synthase, 03 medical and health sciences, chemistry.chemical_compound, Structure-Activity Relationship, Biosynthesis, alpha-aminoacrylate intermediate, ligand-receptor complexes, cysteine synthase complex, transfer difference nmr, anion-binding site, serine acetyltransferase, mycobacterium-tuberculosis, escherichia-coli, gene-expression, 3-dimensional structure, Drug Discovery, Drug Resistance, Bacterial, Structure–activity relationship, Pyridoxal phosphate, chemistry.chemical_classification, Cysteine Synthase, biology, Chemistry, Rational design, Anti-Bacterial Agents, Isoenzymes, 030104 developmental biology, Enzyme, Biochemistry, Pyridoxal Phosphate, biology.protein, Molecular Medicine, Cysteine, Protein Binding |
| الوصف: | Cysteine is a building block for several biomolecules that are crucial for living organisms. The last step of cysteine biosynthesis is catalyzed by O-acetylserine sulfydrylase (OASS)., a highly conserved pyridoxal S'-phosphate (PLP)-dependent enzyme, present in different isoforms in bacteria, plants, and nematodes, but absent in mammals. Beside the biosynthesis of cysteine, OASS exerts a series of "moonlighting" activities in bacteria, such as transcriptional regulation, contact-dependent growth inhibition, swarming motility, and induction of antibiotic resistance. Therefore, the discovery of molecules capable of inhibiting OASS would be a valuable tool to unravel how this protein affects the physiology of unicellular organisms. As a continuation of our efforts toward the synthesis of OASS inhibitors, in this work we have used a combination of computational and spectroscopic approaches to rationally design) synthesize, and test a series of substituted 2-phenylcyclopropane carboxylic acids that bind to the two S. typhymurium OASS isoforms at nanomolar concentrations. |
| تدمد: | 1520-4804 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9017a5c688bd21239305f71f7627cbeb https://pubmed.ncbi.nlm.nih.gov/26894308 |
| حقوق: | RESTRICTED |
| رقم الأكسشن: | edsair.doi.dedup.....9017a5c688bd21239305f71f7627cbeb |
| قاعدة البيانات: | OpenAIRE |
Find this issue from the American Chemical Society | تدمد: | 15204804 |
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