Structure-based screening and design in drug discovery

Drug Discovery Today

Volumn 7, Issue 8, 2002, Pages 471-478

  van Dongen, Maria ^a   Weigelt, Johan ^a   Uppenberg, Jonas ^a   Schultz, Johan ^a   Wikström, Mats ^a  

^a BIOVITRUM AB   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

NEW DRUG; DRUG; LIGAND;

BINDING AFFINITY; CRYSTAL STRUCTURE; DRUG DESIGN; DRUG DEVELOPMENT; DRUG SCREENING; HUMAN; MOLECULAR WEIGHT; NONHUMAN; NUCLEAR MAGNETIC RESONANCE; NUCLEAR OVERHAUSER EFFECT; PHYSICAL CHEMISTRY; REVIEW; STRUCTURE ACTIVITY RELATION; TECHNIQUE; CHEMISTRY; METHODOLOGY; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; SYNTHESIS; X RAY CRYSTALLOGRAPHY;

CRYSTALLOGRAPHY, X-RAY; DRUG DESIGN; DRUG EVALUATION, PRECLINICAL; LIGANDS; MAGNETIC RESONANCE SPECTROSCOPY; PHARMACEUTICAL PREPARATIONS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0037088994     PISSN: 13596446     EISSN: None     Source Type: Journal    
DOI: 10.1016/S1359-6446(02)02233-X     Document Type: Review

References (54)

1. Novel inhibitors of DNA gyrase: 3D structure based biased needle screening, hit validation by biophysical methods, and 3D guide optimization. A promising alternative to random screening
2. The design of leadlike combinatorial libraries
3. Ligand interactions with the Kringle 5 domain of plasminogen
4. One-dimensional relaxation- and diffusion-edited NMR methods for screening compounds that bind to macromolecules
5. Discovering high-affinity ligands for proteins: SAR by NMR
6. Mapping of the binding interfaces of the proteins of the bacterial phosphotransferase system, Hpr and Iia(Glc)
7. Identification of the contact surface of a streptococcal protein G-domain complexed with a human Fc fragment
8. Virtual screening - an overview
9. Structure based focusing of compound libraries
10. Discovery of small-molecule inhibitors of bcl-2 through structure-based computer screening
11. Applications of NMR in drug discovery
12. Library design for NMR-based screening
13. The SHAPES strategy: an NMR-based approach for lead generation in drug discovery
14. Nuclear magnetic resonance-based approaches for lead generation in drug discovery
15. Second-site NMR screening with a spin-labeled first ligand
16. Spin label enhanced NMR screening
17. Cross-correlated F-19 relaxation measurements for the study of fluorinated ligand-receptor interactions
18. Spin diffusion measurements: spin echoes in the presence of a time-dependent field gradient
19. A T(1-Rho)-filtered 2-dimensional transferred noe spectrum for studying antibody interactions with peptide antigens
20. Diffusion-edited NMR - affinity NMR for direct observation of molecular interactions
21. Mixture analysis in combinatorial chemistry. Application of diffusion-resolved NMR spectroscopy
22. Screening mixtures by affinity NMR
23. Mixture analysis by NMR spectroscopy
24. One-dimensional DOSY
25. Theory and application of the transferred nuclear overhauser effect to the study of the conformations of small ligands bound to proteins
26. Conformation of a peptide ligand bound to its G-protein coupled receptor
27. NOE pumping 2, a high-throughput method to determine compounds with binding affinity to macromolecules by NMR
28. NOE pumping: a novel NMR technique for identification of compounds with binding affinity to macromolecules
29. Characterization of ligand binding by saturation transfer difference NMR spectroscopy
30. Identification of compounds with binding affinity to proteins via magnetization transfer from bulk water
31. WaterLOGSY as a method for primary NMR screening: practical aspects and range of applicability
32. Determination of the binding specificity of an integral membrane protein by saturation transfer difference NMR: RGD peptide ligands binding to integrin alpha(IIb)beta(3)
33. 2 relaxation by mutual cancellation of dipole-dipole coupling and chemical shift anisotropy indicate an avenue to NMR structures of very large biological macromolecules in solution
34. 13C-labeled methyl groups
35. Site-selective screening by NMR spectroscopy with labeled amino acid pairs
36. Assignment of the three methionyl carbonyl carbon resonances in Streptomyces subtilisin inhibitor by a carbon-13 and nitrogen-15 double labelling technique. A new strategy for structural studies of proteins in solution
37. Dual amino acid-selective and site-directed stable-isotope labeling of the human c-Ha-Ras protein by cell-free synthesis
38. Heteronuclear NMR experiments
39. Uncoupling of obesity from insulin resistance through a targeted mutation in aP2, the adipocyte fatty acid binding protein
40. Structural studies on human muscle fatty-acid-binding protein at 1.4-Angstrom resolution - binding interactions with 3 C18 fatty-acids
41. NMR-based discovery of lead inhibitors that block DNA binding of the human papillomavirus E2 protein
42. The effects of intermediate exchange processes on the estimation of equilibrium constants by NMR
43. Phosphopeptide binding to the N-terminal Sh2 domain of the P85-α subunit of Pi-3'-kinase - a heteronuclear NMR-study
44. Solution structure and peptide binding of the SH3 domain from human Fyn
45. Protein ligand interactions - exchange processes and determination of ligand conformation and protein ligand contacts
46. Microsecond time scale dynamics in the RXR DNA-binding domain from a combination of spin-echo and off-resonance rotating frame relaxation measurements
47. Direct measurements of the dissociation-rate constant for inhibitor-enzyme complexes via the T-1-Rho and T-2 (Cpmg) methods
48. Discovery of potent nonpeptide inhibitors of stromelysin using SAR by NMR
49. Site-directed ligand discovery
50. The adipocyte lipid-binding protein at 1.6Å resolution - crystal-structures of the apoprotein and with bound saturated and unsaturated fatty-acids
51. Design of adenosine kinase inhibitors from the NMR-based screening of fragments
52. High-throughput nuclear magnetic resonance-based screening
53. Improved sensitivity of HSQC spectra of exchanging protons at short interscan delays using a new fast HSQC (FHSQC) detection scheme that avoids water saturation