title: NMR-based techniques in the hit identification and optimisation processes.
abstract: 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.
authors.affiliation: The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92103, USA. mpellecchia@burnham.org
authors.forename: Maurizio
authors.initials: M
authors.lastname: Pellecchia
authors.forename: Barbara
authors.initials: B
authors.lastname: Becattini
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Crowell
authors.forename: Roberto
authors.initials: R
authors.lastname: Fattorusso
authors.forename: Martino
authors.initials: M
authors.lastname: Forino
authors.forename: Marco
authors.initials: M
authors.lastname: Fragai
authors.forename: Dawoon
authors.initials: D
authors.lastname: Jung
authors.forename: Tomas
authors.initials: T
authors.lastname: Mustelin
authors.forename: Lutz
authors.initials: L
authors.lastname: Tautz
mesh_terms: 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
chemical_list: D004791:Enzyme Inhibitors; D004798:Enzymes; D008024:Ligands