NMR-Guided Fragment-Based Approach for the Design of AAC(6′)-Ib Ligands

Thomas Lombès , Guillaume Bégis (1) , Frédérique Maurice (2) , Serge Turcaud (3) , Thomas Lecourt (4) , Frédéric Dardel (2) , Laurent Micouin (3)

1 SSMIP - Synthèse et structure de molécules d'interet pharmacologique
2 LCRB - UMR 8015 - Laboratoire de cristallographie et RMN biologiques
3 LCBPT - UMR 8601 - Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques
4 COBRA - Chimie Organique et Bioorganique : Réactivité et Analyse

Ligand‐observed NMR experiments have been used to drive the detection and optimisation of non‐aminoglycosidic ligands for AAC(6′)Ib, one of the most clinically important resistance enzymes to aminoglycosides. This fragment‐based approach has been conducted without any need for NMR structural assignment of the target, and has been validated by the preparation of a bisubstrate inhibitor.

Domaines: Chimie organique; Chimie thérapeutique

Thomas Lombès, Guillaume Bégis, Frédérique Maurice, Serge Turcaud, Thomas Lecourt, et al.. NMR-Guided Fragment-Based Approach for the Design of AAC(6′)-Ib Ligands. ChemBioChem, 2008, 9 (9), pp.1368-1371. ⟨10.1002/cbic.200700677⟩. ⟨hal-02185444⟩