Reference : Discovery of New Inhibitors of Resistant Streptococcus pneumoniae Penicillin Binding Pro...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Human health sciences : Immunology & infectious disease
http://hdl.handle.net/2268/24118
Discovery of New Inhibitors of Resistant Streptococcus pneumoniae Penicillin Binding Protein (PBP) 2x by Structure-Based Virtual Screening.
English
Miguet, Laurence [> > > >]
Zervosen, Astrid mailto [Université de Liège - ULg > > Centre de recherches du cyclotron >]
Gerards, Thomas mailto [Université de Liège - ULg > Département des sciences de la vie > Biochimie végétale >]
Pasha, Farhan P [> > > >]
Luxen, André mailto [Université de Liège - ULg > Département de chimie (sciences) > Chimie organique de synthèse - Centre de recherches du cyclotron >]
Disteche-Nguyen, Martine [Université de Liège - ULG > > > > Centre d'Ingénerie des Protéines > >]
Thomas, Aline [> >]
2009
Journal of Medicinal Chemistry
American Chemical Society
Yes (verified by ORBi)
International
0022-2623
1520-4804
Washington
DC
[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
EUR-INTAFAR
Researchers
http://hdl.handle.net/2268/24118
10.1021/jm900625q

File(s) associated to this reference

Fulltext file(s):

FileCommentaryVersionSizeAccess
Restricted access
jm900625q.pdfPublisher postprint1.15 MBRequest copy

Bookmark and Share SFX Query

All documents in ORBi are protected by a user license.