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

Reverse n.O.e. pumping in the detection and optimisation of ligands: 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 ap...

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Bibliographic Details
Published in:Chembiochem : a European journal of chemical biology 2008-06, Vol.9 (9), p.1368-1371
Main Authors: Lombès, Thomas, Bégis, Guillaume, Maurice, Frédérique, Turcaud, Serge, Lecourt, Thomas, Dardel, Frédéric, Micouin, Laurent
Format: Article
Language:English
Subjects:
Acetyltransferases - antagonists & inhibitors
Acetyltransferases - metabolism
aminoglycosides
Aminoglycosides - metabolism
antibiotics
Binding Sites
Chemical Sciences
coenzyme A
Drug Design
Enzyme Inhibitors - chemical synthesis
Enzyme Inhibitors - metabolism
Enzyme Inhibitors - pharmacology
fragment-based synthesis
Ligands
Magnetic Resonance Spectroscopy
Medicinal Chemistry
NMR spectroscopy
Organic chemistry
Protein Binding
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Summary:Reverse n.O.e. pumping in the detection and optimisation of ligands: 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.
ISSN:1439-4227
1439-7633
DOI:10.1002/cbic.200700677