Reference : Synthesis of Modified Peptidoglycan Precursor Analogues for the Inhibition of Glycosy...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/124207
Synthesis of Modified Peptidoglycan Precursor Analogues for the Inhibition of Glycosyltransferase.
English
Dumbre, S [> > > >]
Derouaux, Adeline mailto [Université de Liège - ULg > > Centre d'ingénierie des protéines]
Lescrinier, E [> > > >]
Piette, André [> >]
Joris, Bernard mailto [Université de Liège - ULg > Département des sciences de la vie > Physiologie et génétique bactériennes]
Terrak, Mohammed mailto [Université de Liège - ULg > > Centre d'ingénierie des protéines]
Herdewijn, P [> > > >]
2012
Journal of the American Chemical Society
American Chemical Society
Yes (verified by ORBi)
International
0002-7863
1520-5126
Washington
DC
[en] The peptidoglycan glycosyltransferases (GTs) are essential enzymes that catalyze the polymerization of glycan chains of the bacterial cell wall from lipid II and thus constitute a validated antibacterial target. Their enzymatic cavity is composed of a donor site for the growing glycan chain (where the inhibitor moenomycin binds) and an acceptor site for lipid II substrate. In order to find lead inhibitors able to fill this large active site, we have synthesized a series of substrate analogues of lipid I and lipid II with variations in the lipid, the pyrophosphate, and the peptide moieties and evaluated their biological effect on the GT activity of E. coli PBP1b and their antibacterial potential. We found several compounds able to inhibit the GT activity in vitro and cause growth defect in Bacillus subtilis . The more active was C16-phosphoglycerate-MurNAc-(l-Ala-d-Glu)-GlcNAc, which also showed antibacterial activity. These molecules are promising leads for the design of new antibacterial GT inhibitors.
http://hdl.handle.net/2268/124207
10.1021/ja302099u

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