NMR-based techniques in the hit identification and optimisation processes.
In this review, the use of general NMR spectroscopy techniques to detect ligand binding and to monitor enzyme kinetics and inhibition, which appear particularly useful in hit identification and validation, is reiterated. Furthermore, the use of NMR-based strategies for lead optimisations that are based on either iterative derivatisations of an initial core structure or on linking fragments that occupy adjacent pockets in the target's binding site will also be described. Several recent examples will be reported and the use of these techniques in cases when the three dimensional structure of the target protein is known will be discussed.
Pellecchia
Maurizio
M
The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92103, USA. mpellecchia@burnham.org
Becattini
Barbara
B
Crowell
Kevin J
KJ
Fattorusso
Roberto
R
Forino
Martino
M
Fragai
Marco
M
Jung
Dawoon
D
Mustelin
Tomas
T
Tautz
Lutz
L
D001665:Binding Sites; D003198:Computer Simulation; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004798:Enzymes / Q000378:metabolism; D005544:Forecasting; D007700:Kinetics; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D011485:Protein Binding; D011487:Protein Conformation; D012984:Software; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D004798:Enzymes; D008024:Ligands