Title:Bacterial Transferase MraY, a Source of Inspiration towards New Antibiotics
Volume: 25
Issue: 42
Author(s): Mickaël J. Fer, Laurent Le Corre, Nicolas Pietrancosta, Nathalie Evrard-Todeschi , Samir Olatunji, Ahmed Bouhss, Sandrine Calvet-Vitale*Christine Gravier-Pelletier*
Affiliation:
- Universite Paris Descartes, UMR 8601 CNRS, Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, 45 rue des Saints Peres 75006 Paris,France
- Universite Paris Descartes, UMR 8601 CNRS, Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, 45 rue des Saints Peres 75006 Paris,France
Keywords:
MraY, nucleoside antibiotics, triazoles, molecular modelling, docking, biological evaluations, mutagenesis.
Abstract: The bacterial resistance to antibiotics constitutes more than ever a severe public health problem.
The enzymes involved in bacterial peptidoglycan biosynthesis are pertinent targets for developing
new antibiotics, notably the MraY transferase that is not targeted by any marketed drug. Many research
groups are currently working on the study or the inhibition of this enzyme. After a concise overview of
the role, mechanism and inhibition of MraY, the structure–activity relationships of 5’-triazole-containing
aminoribosyluridine inhibitors, we previously synthetized, will be presented. The recently published
MraY X-ray structures allowed us to achieve a molecular virtual high-throughput screening of commercial
databases and our in-house library resulting in the identification of promising compounds for the further
development of new antibiotics.
