Reference : Structure-based design of benzoxazoles as new inhibitors for D-alanyl-D-alanine ligase
Scientific journals : Article
Human health sciences : Public health, health care sciences & services
http://hdl.handle.net/2268/106777
Structure-based design of benzoxazoles as new inhibitors for D-alanyl-D-alanine ligase
English
Tytgat, Isabelle [Université Catholique de Louvain - UCL > > Unité de Pharmacologie cellulaire et moléculaire > >]
Vandevuer, Stéphane [Université Libre de Bruxelles - ULB > > Structure et fonction des membranes biologiques > >]
Ortmans, Isabelle [Université Libre de Bruxelles - ULB > > structure et fonction des membranes biologiques > >]
Sirockin, Finton [Ecole suprieure de biotechnologie de Strasbourg UMR 7104 > > Laboratoire de biologie et génomique structurales IGBMC > >]
Colacino, Evelina [Université Catholique de Louvain - UCL > > Unité de chimie pharmaceutique et radiopharmacie > >]
Van Bambeke, Françoise [Université Catholique de Louvain - UCL > > Unité de pharmacologie cellulaire et moléculaire > >]
Duez, Colette mailto [Université de Liège - ULg > > Centre d'ingénierie des protéines >]
Poupaert, Jacques H [Université Catholique de Louvain - UCL > > Unité de Chimie pharmaceutique et radiopharmacie > >]
Tulkens, Paul M [Université Catholique de Louvain - UCL > > Unité de Pharmacologie cellulaire et moléculaire > >]
Dejaegere, Annick [Ecole suprieure de biotechnologie de Strasbourg UMR 7104 > > Laboratoire de Biologie et Génomique structurales, IGBMC > >]
Prévost, Martine mailto [Université Libre de Bruxelles - ULB > > Structure et fonction des membranes biologiques > >]
16-Sep-2009
QSAR & Combinatorial Science
Wiley
28
11-12
1394-1404
Yes (verified by ORBi)
International
1611-020X
1611-0218
Weinheim
Germany
[en] Drug Design ; antibiotics ; D-Ala-D-Ala-Ligase
[en] d-Alanyl – d-alanine ligase is an enzyme which catalyzes the dimerization of d-alanine,
and, as such, has an essential role in bacterial cell wall biosynthesis. It has been shown
that inhibition of d-alanyl – d-alanine ligase prevents bacterial growth. d-Alanyl –
d-alanine ligase represents therefore a viable antimicrobial target. The 3D structure of
this enzyme complexed with a phosphinophosphate inhibitor has been reported, which
allows for structure-based design studies. Four softwares (LUDI, MCSS, Autodock, and
Glide) developed either for fragment or full-molecule docking were compared and scored
for their ability to position in the active site four prototypic ligands: two inhibitors, i.e. a
phosphinophosphate derivative and d-cycloserine, d-alanine and d-alanyl – d-alanine.
Best performances were obtained with Glide and MCSS. A short series of novel
derivatives based on a 2-phenylbenzoxazole scaffold was designed de novo on the basis of
computational data. The best compound was found to fully inhibit the d-alanyl –
d-alanine ligase of E. faecalis with an IC50 of 400 mM.
Fonds de la Recherche Scientifique (Communauté française de Belgique) - F.R.S.-FNRS-PAI P5/33-FRSM3.4.597.06.CNRS.INSERM
Researchers ; Professionals
http://hdl.handle.net/2268/106777
10.1002/qsar.200910054

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