Screening assay for inhibitors of a recombinant Streptococcus pneumoniae UDP-glucose pyrophosphorylase

ZAVALA, AGUSTÍN; KOVACEC, VERÓNICA; LEVÍN, GUSTAVO; MOGLIONI, ALBERTINA; MIRANDA, MARÍA VICTORIA; GARCÍA, ERNESTO; BONOFIGLIO, LAURA; MOLLERACH, MARTA

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY

Taylor and Francis

Año: 2017 vol. 32 p. 203 - 207

1475-6366

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.