NMR in the acceleration of drug discovery

Current Opinion in Drug Discovery and Development

Volumn 4, Issue 4, 2001, Pages 479-493

  Sem, D S ^a   Pellecchia, M ^a  

^a Triad Therapeutics Inc   (United States)

Author keywords

Affinity NMR; Diffusion edited; Enzyme mechanomics; Ligand screening; NMR SOLVE; NOE pumping; Nuclear magnetic resonance; Protein structure; Relaxation edited; SAR by NMR; SEA TROSY; SHAPES; Structural genomics; Water LOGSY

Indexed keywords

COMPLEX FORMATION; COST BENEFIT ANALYSIS; DATA BASE; DRUG DESIGN; DRUG DETERMINATION; DRUG EFFICACY; DRUG INDUSTRY; DRUG STRUCTURE; DRUG SYNTHESIS; DYNAMICS; LIGAND BINDING; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PROTEIN BINDING; REVIEW; STRUCTURE ANALYSIS;

ANIMALS; CHEMISTRY, PHARMACEUTICAL; DRUG DESIGN; HUMANS; NUCLEAR MAGNETIC RESONANCE, BIOMOLECULAR; PROTEINS;

EID: 0034918529     PISSN: 13676733     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (49)

1. 2 relaxation by mutual cancellation of dipole-dipole coupling and chemical shift anisotropy indicates an avenue to NMR structures of very large biological macromolecules in solution
2. The second decade-into the third millennium
3. High resolution nuclear magnetic resonance of encapsulated proteins dissolved in low viscosity fluids
4. Solution NMR spectroscopy beyond 25 kDa
5. 13C-labeled methyl groups
6. Improved segmental isotope labeling of proteins and application to a larger protein
7. SEA-TROSY (Solvent Exposed Amides with TROSY): A method to resolve the problem of spectral overlap in very large proteins
8. Protein NMR spectroscopy in structural genomics
9. From structure to function: Approaches and limitations
10. Automated analysis of NMR assignments and structures for proteins
11. Global folds of proteins with low densities of NOEs using residual dipolar couplings: Applications to the 370-residue maltodextrin-binding protein
12. One-dimensional relaxation- and diffusion-edited NMR methods for screening compounds that bind to macromolecules
13. Mixture analysis in combinatorial chemistry. Application of diffusion-resolved NMR spectroscopy
14. Diffusion-edited NMR-affinity NMR for direct observation of molecular interactions
15. NOE pumping: A novel NMR technique for identification of compounds with binding affinity to macromolecules
16. NOE pumping. 2. A high-throughput method to determine compounds with binding affinity to macromolecules by NMR
17. Characterization of ligand binding by saturation transfer difference NMR spectroscopy
18. Detecting binding affinity to immobilized receptor proteins in compound libraries by HR-MAS-STD NMR
19. Identification of compounds with binding affinity to proteins via magnetization transfer from bulk water
20. High-throughput nuclear magnetic resonance-based screening
21. Structure-based design of inhibitors for bacterial thymidylate synthase
22. A TROSY CPMG sequence for characterizing chemical exchange in large proteins
23. Discrete disorder in the nuclear magnetic resonance structure of apo intestinal fatty acid binding protein: Implications for the mechanism of ligand entry
24. 1H exchange
25. The mechanism of phosphodiester hydrolysis: Near in-line attack conformations in the hammerhead ribozyme
26. Solution structure of the transcriptional activation domain of the bacteriophage T4 protein, MotA
27. Discovering high affinity ligands for proteins: SAR by NMR
28. The use of differential chemical shifts for determining the binding site location and orientation of protein-bound ligands
29. Automation of NMR measurements and data evaluation for systematically screening interactions of small molecules with target proteins
30. Automation of measurements and data evaluation in biomolecular NMR screening
31. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings
32. The properties of known drugs. 1. Molecular frameworks
33. Properties of known drugs. 2. Side chains
34. The SHAPES strategy: An NMR-based approach for lead generation in drug discovery
35. High-resolution macromolecular NMR spectroscopy inside living cells
36. Mapping the biochemical trajectory of nephrotoxicity by pattern recognition of NMR urinanalysis
37. 750 MHz HPLC-NMR spectroscopic identification of rat microsomal metabolites of phenoxypyridines
38. Application of hyphenated LC/NMR and LC/MS techniques in rapid identification of in vitro and in vivo metabolites of iloperidone
39. In vivo magnetic resonance methods in pharmaceutical research: Current status and perspectives
40. 2-weighted MRI
41. Monitoring thymidine kinase and ganciclovir-induced changes in rat malignant glioma in vivo by nuclear magnetic resonance imaging
42. 1H MRS detects polyunsaturated fatty acid accumulation during gene therapy of glioma: Implications for the in vivo detection of apoptosis
43. 1H NMR visible lipids in the life and death of cells
44. In vivo three-dimensional reconstruction of rat brain axonal projections by diffusion tensor imaging
45. Millisecond-timescale motions contribute to the function of the bacterial response regulator protein Spo0F
46. Two-state allosteric behavior in a single-domain signaling protein
47. Chemical basis for enzyme catalysis