Reference : Discovery of New Inhibitors of Resistant Streptococcus pneumoniae Penicillin Binding ...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Human health sciences : Immunology & infectious disease
Discovery of New Inhibitors of Resistant Streptococcus pneumoniae Penicillin Binding Protein (PBP) 2x by Structure-Based Virtual Screening.
Miguet, Laurence [> > > >]
Zervosen, Astrid mailto [Université de Liège - ULiège > > Centre de recherches du cyclotron >]
Gerards, Thomas mailto [Université de Liège - ULiège > Département des sciences de la vie > Biochimie végétale >]
Pasha, Farhan P [> > > >]
Luxen, André mailto [Université de Liège - ULiège > Département de chimie (sciences) > Chimie organique de synthèse - Centre de recherches du cyclotron >]
Disteche-Nguyen, Martine [Université de Liège - ULiège > > > > Centre d'Ingénerie des Protéines > >]
Thomas, Aline [> >]
Journal of Medicinal Chemistry
American Chemical Society
Yes (verified by ORBi)
[en] Penicillin binding protein ; resistant S. pneumoniae ; inhibitor ; virtual screening
[en] Penicillin binding proteins (PBPs) are involved in the biosynthesis of the peptidoglycan layer constitutive of the bacterial envelope. They have been targeted for more than half a century by extensively derived molecular scaffolds of penicillins and cephalosporins. Streptococcus pneumoniae resists the antibiotic pressure by inducing highly mutated PBPs that can no longer bind the beta-lactam containing agents. To find inhibitors of PBP2x from Streptococcus pneumoniae (spPBP2x) with novel chemical scaffold so as to circumvent the resistance problems, a hierarchical virtual screening procedure was performed on the NCI database containing approximately 260000 compounds. The calculations involved ligand-based pharmacophore mapping studies and molecular docking simulations in a homology model of spPBP2x from the highly resistant strain 5204. A total of 160 hits were found, and 55 were available for experimental tests. Three compounds harboring two novel chemical scaffolds were identified as inhibitors of the resistant strain 5204-spPBP2x at the micromolar range.
Centre de Recherches du Cyclotron - CRC ; Centre d'Ingénierie des Protéines - CIP

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