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Screening assay for inhibitors of a recombinant Streptococcus pneumoniae UDP-glucose pyrophosphorylase |
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| Authors: | Agustín Zavala Verónica Kovacec Gustavo Levín Albertina Moglioni María Victoria Miranda Ernesto García |
| Institution: | 1. Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Microbiología, Inmunología y Biotecnología, Cátedra de Microbiología, Buenos Aires, Argentina;2. Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Microbiología, Inmunología y Biotecnología, Cátedra de Biotecnología, Buenos Aires, Argentina;3. Departamento de Farmacología, Facultad de Farmacia y Bioquímica, Cátedra de Química Medicinal, Universidad de Buenos Aires, Buenos Aires, Argentina;4. Centro de Investigaciones Biológicas, CSIC and CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain |
| Abstract: | The UDP-glucose pyrophosphorylase of Streptococcus pneumoniae (GalUSpn) is absolutely required for the biosynthesis of capsular polysaccharide, the sine qua non virulence factor of pneumococcus. Since the eukaryotic enzymes are completely unrelated to their prokaryotic counterparts, we propose that the GalU enzyme is a critical target to fight the pneumococcal disease. A recombinant GalUSpn was overexpressed and purified. An enzymatic assay that is rapid, sensitive and easy to perform was developed. This assay was appropriate for screening chemical libraries for searching GalU inhibitors. This work represents a fundamental step in the exploration of novel antipneumococcal drugs. |
| Keywords: | Antibacterial target pneumococcus UTP:glucose 1-phosphate uridylyltransferase virulence inhibitors |