Protein NMR in biomedical research

Cellular and Molecular Life Sciences

Volumn 61, Issue 5, 2004, Pages 580-599

  Jahnke, W ^a   Widmer, H ^a  

^a NOVARTIS PHARMA AG   (Switzerland)

Author keywords

Drug discovery; Fragment based screening; High throughput screening; Hit validation; NMR screening; SAR by NMR; Structure determination

Indexed keywords

ADENOSINE KINASE INHIBITOR; CARBON 13; HUMAN PAPILLOMAVIRUS E2 PROTEIN; LIGAND; MATRIX METALLOPROTEINASE INHIBITOR; NITROGEN 15; PROTEIN; UNCLASSIFIED DRUG; VIRUS PROTEIN;

BINDING AFFINITY; DRUG PROTEIN BINDING; DRUG SCREENING; ENZYME LINKED IMMUNOSORBENT ASSAY; FRAGMENT BASED SCREENING; HIGH THROUGHPUT SCREENING; HIT VALIDATION; ISOTOPE LABELING; LIGAND BINDING; MEDICAL RESEARCH; NONHUMAN; NUCLEAR MAGNETIC RESONANCE; PROTEIN STRUCTURE; PROTON NUCLEAR MAGNETIC RESONANCE; REVIEW; SCREENING; STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS;

HUMAN PAPILLOMAVIRUS; PAPILLOMAVIRUS;

EID: 1642382166     PISSN: 1420682X     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00018-003-3382-3     Document Type: Review

References (140)

1. Rudin M. and Weissleder R. (2003) Molecular imaging in drug discovery and development. Nat. Rev. Drug Discov. 2: 123-131
2. Nicholson J. K., Connelly J., Lindon J. C. and Holmes E. (2002) Metabonomics: a platform for studying drug toxicity and gene function. Nat. Rev. Drug Discov. 1: 153-161
3. Shockcor J. P. and Holmes E. (2002) Metabonomic applications in toxicity screening and disease diagnosis. Curr. Top. Med. Chem. 2: 35-51
4. Stockman B. J. (1998) NMR spectroscopy as a tool for structure-based drug design. Prog. NMR Spectrosc. 33: 109-151
5. Hajduk P. J., Meadows R. P. and Fesik S. W. (1999) NMR-based screening in drug discovery. Q. Rev. Biophys. 32: 211-240
6. Diercks T., Coles M. and Kessler H. (2001) Applications of NMR in drug discovery. Curr. Opin. Chem. Biol. 5: 285-291
7. Peng J. W., Lepre C. A., Fejzo J., Abdul-Manan N. and Moore J. M. (2001) Nuclear magnetic resonance-based approaches for lead generation in drug discovery. Methods Enzymol. 338: 202-230
8. Ross A. and Senn H. (2001) Automation of measurements and data evaluation in biomolecular NMR screening. Drug Discovery Today 6: 583-593
9. Pellecchia M., Sem D. S. and Wuthrich K. (2002) NMR in drug discovery. Nat. Rev. Drug Discov. 1: 211-219
10. Stockman B. J. and Dalvit C. (2002) NMR screening techniques in drug discovery and drug design. Prog. NMR Spectrosc. 41: 187-231
11. Hajduk P. J. and Burns D. J. (2002) Integration of NMR and high-throughput screening. Comb. Chem. High Throughput Screen. 5: 613-621
12. Huth J. R. and Sun C. (2002) Utility of NMR in lead optimization: fragment-based approaches. Comb. Chem. High Throughput Screen. 5: 631-643
13. Wyss D. F., McCoy M. A. and Senior M. M. (2002) NMR-based approaches for lead discovery. Curr. Opin. Drug Discovery Dev. 5: 630-647
14. Zerbe O. (Ed.) (2003) BioNMR in drug research, Wiley, Weinheim
15. Meyer B. and Peters T. (2003) NMR spectroscopy techniques for screening and identifying ligand binding to protein receptors. Angew. Chem. Int. Ed. Engl. 42: 864-890
16. Zartler E. R., Yan J., Mo H., Kline A. D. and Shapiro M. J. (2003) 1D NMR Methods in ligand-receptor interactions. Curr. Top. Med. Chem. 3: 25-37
17. Fejzo J., Lepre C. and Xie X. (2003) Application of NMR screening in drug discovery. Curr. Top. Med. Chem. 3: 81-97
18. Coles M., Heller M. and Kessler H. (2003) NMR-based screening technologies. Drug Discovery Today 8: 803-810
19. Sem D. S. and Pellecchia M. (2001) NMR in the acceleration of drug discovery. Curr. Opin. Drug Discovery Dev. 4: 479-492
20. Shapiro M. J. and Wareing J. R. (1999) High resolution NMR for screening ligand/protein binding. Curr. Opin. Drug Discovery Dev. 2: 396-400
21. Hopkins A. L. and Groom C. R. (2002) The druggable genome. Nat. Rev. Drug Discov. 1: 727-730
22. Kubinyi H. (2003) Drug research: myths, hype and reality. Nat. Rev. Drug Discov. 2: 665-668
23. Clore G. M. and Gronenborn A. M. (1998) NMR structure determination of proteins and protein complexes larger than 20 kDa. Curr. Opin. Chem. Biol. 2: 564-570
24. Staunton D., Owen J. and Campbell I. D. (2003) NMR and structural genomics. Acc. Chem. Res. 36: 207-214
25. Montelione G. T., Zheng D., Huang Y. J., Gunsalus K. C. and Szyperski T. (2000) Protein NMR spectroscopy in structural genomics. Nat. Struct. Biol. 7: 982-985
26. Minn A. J., Velez P. A., Schendel S. L., Liang H., Muchmore S. W., Fesik S. W. et al. (1997) Bcl-xL forms an ion channel in synthetic lipid membranes. Nature 385: 353-357
27. Lomasney J. W., Cheng H.-F., Wang L-P., Kuan Y. S., Liu S. M., Fesik S. W. et al. (1996) Phosphatidylinositol 4,5-bisphosphate binding to the pleckstrin homology domain of phospholipase C-.delta.1 enhances enzyme activity. J. Biol. Chem. 271: 25316-25326
28. Wright P. E. and Dyson H. J. (1999) Intrinsically unstructured proteins: re-assessing the protein structure-function paradigm. J. Mol. Biol. 293: 321-331
29. Fletcher C. M., McGuire A. M., Gingras A. C., Li H., Matsuo H., Sonenberg N. et al. (1998) 4E binding proteins inhibit the translation factor eIF4E without folded structure. Biochemistry 37: 9-15
30. Dames S. A., Martinez-Yamout M., De Guzman R. N., Dyson H. J. and Wright P. E. (2002) Structural basis for Hif-1.alpha./CBP recognition in the cellular hypoxic response. Proc. Natl. Acad. Sci. USA 99: 5271-5276
31. Steinmetz M. O., Kammerer R. A., Jahnke W., Goldie K. N., Lustig A. and Van Oostrum J. (2000) Op18/stathmin caps a kinked protofilament-like tubulin tetramer. EMBO J. 19: 572-580
32. Lepre C. A., Peng J., Fejzo J., Abdul-Manan N., Pocas J., Jacobs M. et al. (2002) Applications of SHAPES screening in drug discovery. Comb. Chem. High Throughput Screen. 5: 583-590
33. Hajduk P. J., Betz S. F., Mack J., Ruan X., Towne D. L., Lerner C. G. et al. (2002) A strategy for high-throughput assay development using leads derived from nuclear magnetic resonance-based screening. J. Biomol. Screen. 7: 429-432
34. Stockman B. J., Farley K. A. and Angwin D. T. (2001) Screening of compound libraries for protein binding using flow-injection nuclear magnetic resonance spectroscopy. Methods Enzymol. 338: 230-246
35. Fischer J. J. and Jardetzky O. (1965) Nuclear magnetic relaxation study of intermolecular complexes. The mechanism of penicillin binding to serum albumin. J. Am. Chem. Soc. 87: 3237-3244
36. Meadows D. H., Roberts G. C. and Jardetzky O. (1969) Nuclear magnetic resonance studies of the structure and binding sites of enzymes. 8. Inhibitor binding to ribonuclease. J. Mol. Biol. 45: 491-511
37. Balaram P., Bothner-By A. A. and Breslow E. (1973) Nuclear magnetic resonance studies of the interaction of peptides and hormones with bovine neurophysin. Biochemistry 12: 4695-4704
38. De Marco A., Laursen R. A. and Llinas M. (1986) 1H-NMR spectroscopic manifestations of ligand binding to the kringle 4 domain of human plasminogen. Arch. Biochem. Biophys. 244: 727-741
39. Hammond S. J., Birdsall B., Feeney J., Searle M. S., Roberts G. C. and Cheung H. T. (1987) Structural comparisons of complexes of methotrexate analogues with Lactobacillus casei dihydrofolate reductase by two-dimensional 1H NMR at 500 MHz. Biochemistry 26: 8585-8590
40. Petros A. M., Ramesh V. and Llinas M. (1989) 1H NMR studies of aliphatic ligand binding to human plasminogen kringle 4. Biochemistry 28: 1368-1376
41. Thewes T., Constantine K., Byeon I. J. and Llinas M. (1990) Ligand interactions with the kringle 5 domain of plasminogen. A study by 1H NMR spectroscopy. J. Biol. Chem. 265: 3906-3915
42. Rejante M. R., Byeon I. J. and Llinas M. (1991) Ligand specificity of human plasminogen kringle 4. Biochemistry 30: 11081-11092
43. Ramesh V, Frederick R. O., Syed S. E., Gibson C. F., Yang J. C. and Roberts G. C. (1994) The interactions of Escherichia coli trp repressor with tryptophan and with an operator oligonucleotide. NMR studies using selectively 15N-labelled protein. Eur. J. Biochem. 225: 601-608
44. Dwek R. A. (1973) Nuclear Magnetic Resonance (N.M.R) in Biochemistry. Applications to enzyme systems, Oxford Univ. Press, New York
45. Jardetzky O. and Roberts G. C. K. (1981) NMR in Molecular Biology, Academic Press, New York
46. Craik D. J. and Higgins K. A. (1990) NMR studies of ligand-macromolecule interactions. Annual Reports on NMR Spectroscopy 22: 61-138
47. Feeney J. (1994) NMR studies of protein ligand interactions. NATO ASI Series, Series H: Cell Biology 87: 115-154
48. Otting G. (1993) Experimental NMR techniques for studies of protein-ligand interactions. Curr. Opin. Struct. Biol. 3: 760-768
49. Shuker S. B., Hajduk P. J., Meadows R. P. and Fesik S. W. (1996) Discovering high-affinity ligands for proteins: SAR by NMR. Science 274: 1531-1534
50. Hajduk P. J., Augeri D. J., Mack J., Mendoza R., Yang J., Betz S. F. et al. (2000) NMR-Based screening of proteins containing 13C-labeled methyl groups. J. Am. Chem. Soc. 122: 7898-7904
51. Yu L., Oost T. K., Schkeryantz J. M., Yang J., Janowick D. and Fesik S. W. (2003) Discovery of aminoglycoside mimetics by NMR-based screening of Escherichia coli A-site RNA. J. Am. Chem. Soc. 125: 4444-4450
52. Hajduk P. J., Olejniczak E. T. and Fesik S. W (1997) One-dimensional relaxation-and diffusion-edited NMR methods for screening compounds that bind to macromolecules. J. Am. Chem. Soc. 119: 12257-12261
53. Jahnke W., Ruedisser S. and Zurini M. (2001) Spin label enhanced NMR screening. J. Am. Chem. Soc. 123: 3149-3150
54. Chen A. and Shapiro M. J. (1999) Affinity NMR. Anal. Chem. 71: 669A-675A
55. Lian L. Y., Barsukov I. L., Sutcliffe M. J., Sze K. H. and Roberts G. C. (1994) Protein-ligand interactions: exchange processes and determination of ligand conformation and protein-ligand contacts. Methods Enzymol. 239: 657-700
56. Meyer B., Weimar T. and Peters T. (1997) Screening mixtures for biological activity by NMR. Eur. J. Biochem. 246: 705-709
57. Mayer M. and Meyer B. (1999) Characterization of ligand binding by saturation transfer difference NMR spectroscopy. Angew. Chem. Int. Ed. Engl. 38: 1784-1788
58. Dalvit C., Pevarello P., Tato M., Veronesi M., Vulpetti A. and Sundstrom M. (2000) Identification of compounds with binding affinity to proteins via magnetization transfer from bulk water. J. Biomol. NMR. 18: 65-68
59. Chen A. and Shapiro M. J. (2000) NOE pumping as high-throughput method to determine compounds with binding affinity to macromolecules by NMR. J. Am. Chem. Soc. 122: 414-415
60. Klein J., Meinecke R., Mayer M. and Meyer B. (1999) Detecting binding affinity to immobilized receptor proteins in compound libraries by HR-MAS STD NMR. J. Am. Chem. Soc. 121: 5336-5337
61. Meinecke R. and Meyer B. (2001) Determination of the binding specificity of an integral membrane protein by saturation transfer difference NMR: RGD peptide ligands binding to integrin alphaIIbbeta3. J. Med. Chem. 44: 3059-3065
62. Benie A. J., Moser R., Bauml E., Blaas D and Peters T. (2003) Virus-ligand interactions: identification and characterization of ligand binding by NMR spectroscopy. J. Am. Chem. Soc. 125: 14-15
63. Mayer M. and James T. L. (2002) Detecting ligand binding to a small RNA target via saturation transfer difference NMR experiments in D(2)O and H(2)O. J. Am. Chem. Soc. 124: 13376-13377
64. Dalvit C., Flocco M., Knapp S., Mostardini M., Perego R., Stockman B. J. et al. (2002) High-throughput NMR-based screening with competition binding experiments. J. Am. Chem. Soc. 124: 7702-7709
65. Jahnke W., Floersheim P., Ostermeier C., Zhang X., Hemmig R., Hurth K. et al. (2002) NMR reporter screening for the detection of high-affinity ligands. Angew. Chem. Int. Ed. Engl. 41: 3420-3423
66. Siriwardena A. H., Tian F., Noble S. and Prestegard J. H. (2002) A straightforward NMR-spectroscopy-based method for rapid library screening. Angew. Chem. Int. Ed. Engl. 41: 3454-3457
67. Mayer M. and Meyer B. (2000) Mapping the active site of angiotensin-converting enzyme by transferred NOE spectroscopy. J. Med. Chem. 43: 2093-2099
68. Peng J. W. (2001) Cross-correlated 19F relaxation measurements for the study of fluorinated ligand-receptor interactions. J. Magn. Reson. 153: 32-47
69. Dalvit C., Flocco M., Veronesi M. and Stockman B. J. (2002) Fluorine-NMR competition binding experiments for high-throughput screening of large compound mixtures. Comb. Chem. High Throughput Screen. 5: 605-611
70. Dalvit C., Fagerness P. E., Hadden D. T., Sarver R. W. and Stockman B. J. (2003) Fluorine-NMR experiments for high-throughput screening: theoretical aspects, practical considerations and range of applicability. J. Am. Chem. Soc. 125: 7696-7703
71. Mayer M. and Meyer B. (2001) Group epitope mapping by saturation transfer difference NMR to identify segments of a ligand in direct contact with a protein receptor. J. Am. Chem. Soc. 123: 6108-6117
72. Dalvit C., Fasolini M., Flocco M., Knapp S., Pevarello P. and Veronesi M. (2002) NMR-based screening with competition water-ligand observed via gradient spectroscopy experiments: detection of high-affinity ligands. J. Med. Chem. 45: 2610-2614
73. Yan J., Kline A. D., Mo H., Shapiro M. J. and Zartler E. R. (2003) The effect of relaxation on the epitope mapping by saturation transfer difference NMR. J. Magn. Reson. 163: 270-276
74. Rossi C., Donati A. and Sansoni M. R. (1992) Nuclear magnetic resonance as a tool for the identification of specific DNA-ligand interaction. Chem. Phys. Lett. 189: 278-280
75. Lepre C. A. (2001) Library design for NMR-based screening. Drug Discovery Today 6: 133-140
76. Lepre C. (2003) Strategies for NMR screening and library design. In: BioNMR in Drug Research, pp. 391-415, Zerbe O. (ed.), Wiley, Weinheim
77. Jacoby E., Davies J. and Blommers M. J. (2003) Design of small molecule libraries for NMR screening and other applications in drug discovery. Curr. Top. Med. Chem. 3: 11-23
78. Hann M. M., Leach A. R. and Harper G. (2001) Molecular complexity and its impact on the probability of finding leads for drug discovery. J. Chem. Inf. Comput. Sci. 41: 856-864
79. Jahnke W., Florsheimer A., Blommers M. J., Paris C. G., Heim J., Nalin C. M. et al. (2003) Second-site NMR screening and linker design. Curr. Top. Med. Chem. 3: 69-80
80. Rudisser S. and Jahnke W. (2002) NMR and in silico screening. Comb. Chem. High Throughput Screen. 5: 591-603
81. Verlinde C. L. M. J., Rudenko G. and Hol W. G. J. (1992) In search of new lead compounds for trypanosomiasis drug design: a protein structure-based linked-fragment approach. J. Comput.-Aided Mol. Des. 6: 131-147
82. Hajduk P. J., Sheppard G., Nettesheim D. G., Olejniczak E. T., Shuker S. B., Meadows R. P. et al. (1997) Discovery of potent nonpeptide inhibitors of stromelysin using SAR by NMR. J. Am. Chem. Soc. 119: 5818-5827
83. Olejniczak E. T., Hajduk P. J., Marcotte P. A., Nettesheim D. G., Meadows R. P., Edalji R. et al. (1997) Stromelysin inhibitors designed from weakly bound fragments: effects of linking and cooperativity. J. Am. Chem. Soc. 119: 5828-5832
84. Szczepankiewicz B. G., Liu G., Hajduk P. J., Abad-Zapatero C., Pei Z., Xin Z. et al. (2003) Discovery of a potent, selective protein tyrosine phosphatase IB inhibitor using a linked-fragment strategy. J. Am. Chem. Soc. 125: 4087-4096
85. Hajduk P. J., Dinges J., Miknis G. F., Merlock M., Middleton T., Kempf D. J. et al. (1997) NMR-based discovery of lead inhibitors that block DNA binding of the human papillomavirus E2 protein. J. Med. Chem. 40: 3144-3150
86. Bohacek R. S., McMartin C. and Guida W. C. (1996) The art and practice of structure-based drug design: a molecular modeling perspective. Med. Res. Rev. 16: 3-50
87. Hajduk P. J., Dinges J., Schkeryantz J. M., Janowick D., Kaminski M., Tufano M. et al. (1999) Novel inhibitors of Erm methyltransferases from NMR and parallel synthesis. J. Med. Chem. 42: 3852-3859
88. Pellecchia M., Meininger D., Dong Q., Chang E., Jack R. and Sem D. S. (2002) NMR-based structural characterization of large protein-ligand interactions. J. Biomol. NMR 22: 165-173
89. Hajduk P. J., Boyd S., Nettesheim D., Nienaber V., Severin J., Smith R. et al. (2000) Identification of novel inhibitors of urokinase via NMR-based screening. J. Med. Chem. 43: 3862-3866
90. Van Dongen M. J. P., Uppenberg J., Svensson S., Lundbaeck T., Kerud T., Wikstroem M. et al. (2002) Structure-based screening as applied to human FABP4: a highly efficient alternative to HTS for hit generation. J. Am. Chem. Soc. 124: 11874-11880
91. Fejzo J., Lepre C. A., Peng J. W., Bemis G. W., Ajay, Murcko M. A. et al. (1999) The SHAPES strategy: an NMR-based approach for lead generation in drug discovery. Chem. Biol. 6: 755-769
92. Fabbro D., Ruetz S., Buchdunger E., Cowan-Jacob S. W., Fendrich G., Liebetanz J. et al. (2002) Protein kinases as targets for anticancer agents: from inhibitors to useful drugs. Pharmacol. Ther. 93: 79-98
93. Traxler P. (2003) Tyrosine kinases as targets in cancer therapy - successes and failures. Expert Opin. Ther. Targets. 7: 215-234
94. Capdeville R., Buchdunger E., Zimmermann J. and Matter A. (2002) Glivec (STI571, imatinib), a rationally developed, targeted anticancer drug. Nat. Rev. Drug Discov. 1: 493-502
95. Traxler P. and Furet P. (1999) Strategies toward the design of novel and selective protein tyrosine kinase inhibitors. Pharmacol. Ther. 82: 195-206
96. Blundell T. L., Jhoti H. and Abell C. (2002) High-throughput crystallography for lead discovery in drug design. Nat. Rev. Drug Discov. 1: 45-54
97. Swayze E. E., Jefferson E. A., Sannes-Lowery K. A., Blyn L. B., Risen L. M., Arakawa S. et al. (2002) SAR by MS: a ligand based technique for drug lead discovery against structured RNA targets. J. Med. Chem. 45: 3816-3819
98. Moy F. J., Haraki K., Mobilio D., Walker G., Powers R., Tabei K. et al. (2001) MS/NMR: a structure-based approach for discovering protein ligands and for drug design by coupling size exclusion chromatography, mass spectrometry and nuclear magnetic resonance spectroscopy. Anal. Chem. 73: 571-581
99. Abagyan R. and Totrov M. (2001) High-throughput docking for lead generation. Curr. Opin. Chem. Biol. 5: 375-382
100. Braisted A. C., Oslob J. D., Delano W. L., Hyde J., McDowell R. S., Waal N. et al. (2003) Discovery of a potent small molecule IL-2 inhibitor through fragment assembly. J. Am. Chem. Soc. 125: 3714-3715
101. Boehm H.-J., Boehringer M., Bur D., Gmuender H., Huber W., Klaus W. et al. (2000) Novel inhibitors of DNA gyrase: 3D structure based biased needle screening, hit validation by biophysical methods and 3D guided optimization. A promising alternative to random screening. J. Med. Chem. 43: 2664-2674
102. Lewis W. G., Green L. G., Grynszpan F., Radic Z., Carlier P. R., Taylor P. et al. (2002) Click chemistry in situ: acetylcholinesterase as a reaction vessel for the selective assembly of a femtomolar inhibitor from an array of building blocks. Angew. Chem. Int. Ed. Engl. 41: 1053-1057
103. Otto S., Furlan R. L. and Sanders J. K. (2002) Recent developments in dynamic combinatorial chemistry. Curr. Opin. Chem. Biol. 6: 321-327
104. Maly D. J., Choong I. C. and Ellman J. A. (2000) Combinatorial target-guided ligand assembly: identification of potent subtype-selective c-Src inhibitors. Proc. Natl. Acad. Sci. USA 97: 2419-2424
105. Ramstrom O. and Lehn J. M. (2002) Drug discovery by dynamic combinatorial libraries. Nat. Rev. Drug Discov. 1: 26-36
106. Kubinyi H. (1998) Structure-based drug design. Chimica Oggi 16: 17-22
107. Kubinyi H. (1998) Combinatorial and computational approaches in structure-based drug design. Curr. Opin. Drug Discovery Dev. 1: 16-27
108. Wüthrich K. (1995) NMR - this other method for protein and nucleic acid structure determination. Acta Crystallogr. D. Biol. Crystallogr. D51: 249-270
109. Ni F. (1994) Recent developments in transferred NOE methods. Prog. NMR Spectrosc. 26: 517-606
110. Carlomagno T., Felli I. C., Czech M., Fischer R., Sprinzl M. and Griesinger C. (1999) Transferred cross-correlated relaxation: application to the determination of sugar pucker in an aminoacylated tRNA-mimetic weakly bound to EF-Tu. J. Am. Chem. Soc. 121: 1945-1948
111. Blommers M. J. J., Stark W., Jones C. E., Head D., Owen C. E. and Jahnke W. (1999) Transferred cross-correlated relaxation complements transferred NOE: Structure of an IL-4R-derived peptide bound to STAT-6. J. Am. Chem. Soc. 121: 1949-1953
112. Carlomagno T., Blommers M. J., Meiler J., Jahnke W., Schupp T., Petersen F. et al. (2003) The high-resolution solution structure of epothilone A bound to tubulin: an understanding of the structure-activity relationships for a powerful class of antitumor Agents. Angew. Chem. Int. Ed. Engl. 42: 2511-2515
113. Peng J. W. (2003) New probes of ligand flexibility in drug design: transferred (13)C CSA-dipolar cross-correlated relaxation at natural abundance. J. Am. Chem. Soc. 125: 11116-11130
114. McCoy M. A. and Wyss D. F. (2002) Spatial localization of ligand binding sites from electron current density surfaces calculated from NMR chemical shift perturbations. J. Am. Chem. Soc. 124: 11758-11763
115. Gargaro A. R., Frenkiel T. A., Nieto P. M., Birdsall B., Polshakov V. I., Morgan W. D. et al. (1996) NMR detection of arginine-ligand interactions in complexes of Lactobacillus casei dihydrofolate reductase. Eur. J. Biochem. 238: 435-439
116. Grzesiek S., Cordier F. and Dingley A. J. (2001) Scalar couplings across hydrogen bonds. Methods Enzymol. 338: 111-133
117. Kessler H. (1982) Peptide conformations. Part 19. Conformation and biological effects of cyclic peptides. Angew. Chem. 94: 509-520
118. 3 integrin for a new cancer therapy. Angew. Chem. Int. Ed. Engl. 36: 1374-1389
119. Gottschalk K.-E. and Kessler H. (2002) The structures of integrins and integrin-ligand complexes: implications for drug design and signal transduction. Angew. Chem. Int. Ed. Engl. 41: 3767-3774
120. 3 integrin antagonists. J. Med. Chem. 42: 3033-3040
121. 7-integrin antagonists from cyclic peptides. Angew. Chem. Int. Ed. Engl. 41: 3007-3011
122. Peng J. W. and Wagner G. (1994) Investigation of protein motions via relaxation measurements. Methods Enzymol. 239: 563-596
123. Palmer A. G. III, Kroenke C. D. and Loria J. P. (2001) Nuclear magnetic resonance methods for quantifying microsecond-to-millisecond motions in biological macromolecules. Methods Enzymol. 339: 204-238
124. Kay L. E. (1998) Protein dynamics from NMR. Nat. Struct. Biol. 5: 513-517
125. Fushman D. and Cowburn D. (2001) Nuclear magnetic resonance relaxation in determination of residue-specific 15N chemical shift tensors in proteins in solution: protein dynamics, structure and applications of transverse relaxation optimized spectroscopy. Methods Enzymol. 339: 109-126
126. Skrynnikov N. R., Millet O. and Kay L. E. (2002) Deuterium spin probes of side-chain dynamics in proteins. 2. Spectral density mapping and identification of nanosecond time-scale side-chain motions. J. Am. Chem. Soc. 124: 6449-6460
127. Stone M. J. (2001) NMR relaxation studies of the role of conformational entropy in protein stability and ligand binding. Ace. Chem. Res. 34: 379-388
128. Zidek L., Novotny M. V. and Stone M. J. (1999) Increased protein backbone conformational entropy upon hydrophobic ligand binding. Nat. Struct. Biol. 6: 1118-1121
129. Moy F. J., Chanda P. K., Chen J., Cosmi S., Edris W., Levin J. I. et al. (2002) Impact of mobility on structure-based drug design for the MMPs. J. Am. Chem. Soc. 124: 12658-12659
130. Hajduk P. J., Gomtsyan A., Didomenico S., Cowart M., Bayburt E. K., Solomon L. et al. (2000) Design of adenosine kinase inhibitors from the NMR-based screening of fragments. J. Med. Chem. 43: 4781-4786
131. Hajduk P. J., Shuker S. B., Nettesheim D. G., Craig R., Augeri D. J., Betebenner D. et al. (2002) NMR-based modification of matrix metalloproteinase inhibitors with improved bioavailability. J. Med. Chem. 45: 5628-5639
132. Peters T. Jr(1996) AU about Albumin: Biochemistry, Genetics and Medical Applications, Academic Press, San Diego
133. Mao H., Hajduk P. J., Craig R., Bell R., Borre T. and Fesik S. W. (2001) Rational design of diflunisal analogues with reduced affinity for human serum albumin. J. Am. Chem. Soc. 123: 10429-10435
134. Dalvit C., Flocco M., Stockman B. J. and Veronesi M. (2002) Competition binding experiments for rapidly ranking lead molecules for their binding affinity to human serum albumin. Comb. Chem. High Throughput Screen. 5: 645-650
135. Dalvit C., Hadden D. T., Sarver R. W., Ho A. M. and Stockman B. J. (2003) Multi-selective one dimensional proton NMR experiments for rapid screening and binding affinity measurements. Comb Chem High Throughput Screen. 6: 445-453
136. Wada C. K., Holms J. H., Curtin M. L., Dai Y., Florjancic A. S., Garland R. B. et al. (2002) Phenoxyphenyl sulfone N-formylhydroxylamines (retrohydroxamates) as potent, selective, orally bioavailable matrix metalloproteinase inhibitors. J. Med. Chem. 45: 219-232
137. Liu G., Huth J. R., Olejniczak E. T., Mendoza R., DeVries P., Leitza S. et al. (2001) Novel p-arylthio cinnamides as antagonists of leukocyte function-associated antigen-1/intracellular adhesion molecule-1 interaction. 2. Mechanism of inhibition and structure-based improvement of pharmaceutical properties. J. Med. Chem. 44: 1202-1210
138. Pervushin K. V. (2003) Transverse relaxation optimized spectroscopy. Biological Magnetic Resonance 20: 3-34
139. Wüthrich K. and Wider G. (2002) Transverse relaxation-optimized NMR spectroscopy with biomacromolecular structures in solution. Encyclopedia of Nuclear Magnetic Resonance 9: 468-477
140. Tugarinov V., Muhandiram R., Ayed A. and Kay L. E. (2002) Four-dimensional NMR spectroscopy of a 723-residue protein: chemical shift assignments and secondary structure of malate synthase G. J. Am. Chem. Soc. 124: 10025-10035