NMR identification of ligands of aminoglycoside resistance enzymes

Frédérique Maurice (1) , Guillaume Bégis (2) , Laurent Micouin (2) , Frédéric Dardel (1)

1 LCRB - UMR 8015 - Laboratoire de cristallographie et RMN biologiques
2 SSMIP - Synthèse et structure de molécules d'interet pharmacologique

Bacterial resistance to aminoglycosides is mainly the result of enzyme-catalyzed chemical modifications of these antibiotics, which prevents their binding to their target. In order to circumvent this mechanism, an attractive possibility would be to block these enzymes, using selective inhibitors. This work describes a rational strategy aimed at isolating specific ligands of these enzymes, using NMR spectroscopy. Using magnetization transfer techniques, the identification of contacts between elementary pharmacophores and the protein target allows the guidance of hit improvement from a very early stage.

Mots clés: flow-injection NMR; screening; antibiotic; deoxystreptamine; fluorescence

Domaines: Biochimie, Biologie Moléculaire

Frédérique Maurice, Guillaume Bégis, Laurent Micouin, Frédéric Dardel. NMR identification of ligands of aminoglycoside resistance enzymes. Comptes Rendus. Chimie, 2006, 9, pp.413-419. ⟨hal-00021873⟩