Bacterial Transferase MraY, a Source of Inspiration towards New Antibiotics

Mickaël Fer (1) , Laurent Le Corre (1) , Nicolas Pietrancosta (1, 2, 3) , Nathalie Evrard-Todeschi (1) , Samir Olatunji (4) , Ahmed Bouhss (4, 5) , Sandrine Calvet-Vitale (1) , Christine Gravier-Pelletier (1)

1 LCBPT - UMR 8601 - Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques
2 NPS - Systèmes glutamatergiques normaux et pathologiques = Normal and Pathologic Glutamatergic Neurons
3 LBM-E2 - Analyse, Interactions Moléculaires et Cellulaires
4 I2BC - Institut de Biologie Intégrative de la Cellule
5 SABNP - Structure et activité des biomolécules normales et pathologiques

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.

Keywords: Triazoles; MraY; Biological evaluations; Docking; Molecular modelling; Mutagenesis; Nucleoside antibiotics

Domains: Organic chemistry; Medicinal Chemistry; Life Sciences [q-bio]

Mickaël Fer, Laurent Le Corre, Nicolas Pietrancosta, Nathalie Evrard-Todeschi, Samir Olatunji, et al.. Bacterial Transferase MraY, a Source of Inspiration towards New Antibiotics. Current Medicinal Chemistry, 2018, 25 (42), pp.6013-6029. ⟨10.2174/0929867325666180330095154⟩. ⟨hal-02364241⟩