Tethering

Fragment-based Approaches in Drug Discovery

Volumn 34, Issue , 2006, Pages 285-310

  Erlanson, Daniel A ^a   Ballinger, Marcus D ^b   Wells, James A ^c  

^a Marquette University   (United States)

^b Sunesis Pharmaceuticals Inc   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Disulfide formation; Drug discovery; Energetics of fragment selection in tethering; Experimental applications; Experimental techniques; Finding fragments; Imine formation; Linking fragments; Metal mediated; Practical considerations; Related approaches; Tethering

Indexed keywords

AMINO ACIDS; PROTEINS; SULFUR COMPOUNDS;

DISULFIDE FORMATION; DRUG DISCOVERY; EXPERIMENTAL APPLICATION; EXPERIMENTAL TECHNIQUES; FINDING FRAGMENTS; FRAGMENT SELECTIONS; IMINE FORMATION; LINKING FRAGMENTS; PRACTICAL CONSIDERATIONS; RELATED APPROACHES; TETHERING;

SITE SELECTION;

EID: 84896955341     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1002/3527608761.ch14     Document Type: Chapter

References (51)

1. Tethering is a service mark of Sunesis Pharmaceuticals, Inc. for its fragment-based drug discovery.
2. Erlanson, D. A., Wells, J. A., Braisted, A. C. 2004, Tethering: Fragment-based drug discovery. Annu. Rev. Biophys. Biomol. Struct. 33, 199-223.
3. Murray, C. W., Verdonk, M. L. 2002, The consequences of translational and rotational entropy lost by small molecules on binding to proteins. J. Comput. Aided Mol. Des. 16, 741-753.
4. Hyde, J., Braisted, A. C., Randal, M., Arkin, M. R. 2003, Discovery and characterization of cooperative ligand binding in the adaptive region of interleukin-2. Biochemistry 42, 6475-6483.
5. Keire, D. A., Strauss, E., Guo, W., Noszál, B., Rabenstein, D. L. 1992, Kinetics and equilibria of thiol/disulfide interchange reactions of selected biological thiols and related molecules with oxidized glutathione. J. Org. Chem. 57, 123-127.
6. Millis, K. K., Weaver, K. H., Rabenstein, D. L. 1993, Oxidation/reduction potential of glutathione. J. Org. Chem. 58, 4144-4146.
7. Mammen, M., Shakhnovich, E. I., Whitesides, G. M. 1998, Using a convenient, quantitative model for torsional entropy to establish qualitative trends for molecular processes that restrict conformational freedom. J. Org. Chem. 63, 3168-3175.
8. Zhou, H. X. 2001, The affinity-enhancing roles of flexible linkers in two-domain DNA-binding proteins. Biochemistry 40, 15069-15073.
9. Zhou, H. X. 2003, Quantitative account of the enhanced affinity of two linked scFvs specific for different epitopes on the same antigen. J. Mol. Biol. 329, 1-8.
10. McGovern, S. L., Caselli, E., Grigorieff, N., Shoichet, B. K. 2002, A common mechanism underlying promiscuous inhibitors from virtual and high-throughput screening. J. Med. Chem. 45, 1712-1722.
11. Costi, M. P., Tondi, D., Rinaldi, M., Barlocco, D., Pecorari, P., Soragni, F., Venturelli, A., Stroud, R. M. 2002, Structure-based studies on species-specific inhibition of thymidylate synthase. Biochim. Biophys. Acta 1587, 206-214.
12. Erlanson, D. A., Braisted, A. C., Raphael, D. R., Randal, M., Stroud, R. M., Gordon, E. M., Wells, J. A. 2000, Site-directed ligand discovery. Proc. Natl. Acad. Sci. USA 97, 9367-9372.
13. Johnson, T. O., Ermolieff, J., Jirousek, M. R. 2002, Protein tyrosine phosphatase 1B inhibitors for diabetes. Nat. Rev. Drug Discov. 1, 696-709.
14. Erlanson, D. A., McDowell, R. S., He, M. M., Randal, M., Simmons, R. L., Kung, J., Waight, A., Hansen, S. K. 2003, Discovery of a new phosphotyrosine mimetic for PTP1B using breakaway tethering. J. Am. Chem. Soc. 125, 5602-5603.
15. Clackson, T., Wells, J. A. 1995, A hot spot of binding energy in a hormone-receptor interface. Science 267, 383-386.
16. DeLano, W. L. 2002, Unraveling hot spots in binding interfaces: progress and challenges. Curr. Opin. Struct. Biol. 12, 14-20.
17. Arkin, M. R., Wells, J. A. 2004, Small-molecule inhibitors of protein-protein interactions: progressing towards the dream. Nat. Rev. Drug. Discov. 3, 301-317.
18. Tilley, J. W., Chen, L., Fry, D. C., Emerson, S. D., Powers, G. D., Biondi, D., Varnell, T., Trilles, R., et al. 1997, Identification of a small molecule inhibitor of the IL-2/IL-2Ra receptor interaction which binds to IL-2. J. Am. Chem. Soc. 119, 7589-7590.
19. Arkin, M. R., Randal, M., DeLano, W. L., Hyde, J., Luong, T. N., Oslob, J. D., Raphael, D. R., Taylor, L., et al. 2003, Binding of small molecules to an adaptive protein-protein interface. Proc. Natl. Acad. Sci. USA 100, 1603-1608.
20. Braisted, A. C., Oslob, J. D., Delano, W. L., Hyde, J., McDowell, R. S., Waal, N., Yu, C., Arkin, M. R., et al. 2003, Discovery of a potent small molecule IL-2 inhibitor through fragment assembly. J. Am. Chem. Soc. 125, 3714-3715.
21. Raimundo, B. C., Oslob, J. D., Braisted, A. C., Hyde, J., McDowell, R. S., Randal, M., Waal, N. D., Wilkinson, J., et al. 2004, Integrating fragment assembly and biophysical methods in the chemical advancement of small-molecule antagonists of IL-2: an approach for inhibiting protein-protein interactions. J. Med. Chem. 47, 3111-3130.
22. Waal, N. D., Yang, W., Oslob, J. D., Arkin, M. R., Hyde, J., Lu, W., McDowell, R. S., Yu, C. H., et al. 2005, Identification of nonpeptidic small-molecule inhibitors of interleukin-2. Bioorg. Med. Chem. Lett. 15, 983-987.
23. Thanos, C. D., Randal, M., Wells, J. A. 2003, Potent small-molecule binding to a dynamic hot spot on IL-2. J. Am. Chem. Soc. 125, 15280-15281.
24. Erlanson, D. A., Lam, J. W., Wiesmann, C., Luong, T. N., Simmons, R. L., DeLano, W. L., Choong, I. C., Burdett, M. T., et al. 2003, In situ assembly of enzyme inhibitors using extended tethering. Nat. Biotechnol. 21, 308-314.
25. O'Brien, T., Lee, D. 2004, Prospects for caspase inhibitors. Mini. Rev. Med. Chem. 4, 153-165.
26. Choong, I. C., Lew, W., Lee, D., Pham, P., Burdett, M. T., Lam, J. W., Wiesmann, C., Luong, T. N., et al. 2002, Identification of potent and selective small-molecule inhibitors of caspase-3 through the use of extended tethering and structure-based drug design. J. Med. Chem. 45, 5005-5022.
27. Allen, D. A., Pham, P., Choong, I. C., Fahr, B., Burdett, M. T., Lew, W., DeLano, W. L., Gordon, E. M., et al. 2003, Identification of potent and novel small-molecule inhibitors of caspase-3. Bioorg. Med. Chem. Lett. 13, 3651-3655.
28. O'Brien, T., Fahr, B. T., Sopko, M., Lam, J. W., Waal, N. D., Raimundo, B. C., Purkey, H., Pham, P., et al. 2005, Structural analysis of caspase-1 inhibitors derived from Tethering. Acta Crystallogr. F61, 451-458.
29. Thornberry, N. A., Rano, T. A., Peterson, E. P., Rasper, D. M., Timkey, T., Garcia-Calvo, M., Houtzager, V., Nordstrom, P., et al. 1997, A combinatorial approach defines specificities of members of the caspase family and Granzyme B. J. Biol. Chem. 272, 17907-17911.
30. Hardy, J. A., Lam, J., Nguyen, J. T., O'Brien, T., Wells, J. A. 2004, Discovery of an allosteric site in the caspases. Proc. Natl. Acad. Sci. USA 101, 12461-12466.
31. Fuentes-Prior, P., Salvesen, G. S. 2004, The protein structures that shape caspase activity, specificity, activation and inhibition. Biochem. J. 384, 201-232.
32. Romanowski, M. J., Scheer, J. M., O'Brien, T., McDowell, R. S. 2004, Crystal structures of a ligand-free and malonate-bound human caspase-1: implications for the mechanism of substrate binding. Structure 12, 1361-1371.
33. Hardy, J. A., Wells, J. A. 2004, Searching for new allosteric sites in enzymes. Curr. Opin. Struct. Biol. 14, 706-715.
34. Buck, E., Bourne, H., Wells, J. A. 2005, Site-specific disulfide capture of agonist and antagonist peptides on the C5 a receptor. J. Biol. Chem. 280, 4009-4012.
35. Palczewski, K., Kumasaka, T., Hori, T., Behnke, C. A., Motoshima, H., Fox, B. A., Le Trong, I., Teller, D. C., et al. 2000, Crystal structure of rhodopsin: A G protein-coupled receptor. Science 289, 739-745.
36. Gerber, B. O., Meng, E. C., Dotsch, V., Baranski, T. J., Bourne, H. R. 2001, An activation switch in the ligand binding pocket of the C5 a receptor. J. Biol. Chem. 276, 3394-3400.
37. Buck, E., Wells, J. A. 2005, Disulfide trapping to localize small-molecule agonists and antagonists for a G protein-coupled receptor. Proc. Natl. Acad. Sci. USA 102, 2719-24.
38. Cohen, G. B., Oprian, D. D., Robinson, P. R. 1992, Mechanism of activation and inactivation of opsin: role of Glu113 and Lys296. Biochemistry 31, 12592-12601.
39. Erlanson, D. A., Hansen, S. K. 2004, Making drugs on proteins: site-directed ligand discovery for fragment-based lead assembly. Curr. Opin. Chem. Biol. 8, 399-406.
40. Wiseman, R. L., Johnson, S. M., Kelker, M. S., Foss, T., Wilson, I. A., Kelly, J. W. 2005, Kinetic stabilization of an oligomeric protein by a single ligand binding event. J. Am. Chem. Soc. 127, 5540-5551.
41. Abe, Y., Shodai, T., Muto, T., Mihara, K., Torii, H., Nishikawa, S., Endo, T., Kohda, D. 2000, Structural basis of presequence recognition by the mitochondrial protein import receptor Tom20. Cell 100, 551-560.
42. Obita, T., Muto, T., Endo, T., Kohda, D. 2003, Peptide library approach with a disulfide tether to refine the Tom20 recognition motif in mitochondrial presequences. J. Mol. Biol. 328, 495-504.
43. Webb, M. E., Stephens, E., Smith, A. G., Abell, C. 2003, Rapid screening by MALDI-TOF mass spectrometry to probe binding specificity at enzyme active sites. Chem. Commun. 2003, 2416-2417.
44. Vincent, F., Openshaw, M., Trautwein, M., Gaskell, S. J., Kohn, H., Widger, W. R. 2000, Rho transcription factor: symmetry and binding of bicyclomycin. Biochemistry 39, 9077-9083.
45. Vincent, F., Widger, W. R., Openshaw, M., Gaskell, S. J., Kohn, H. 2000, 5a-formylbicyclomycin: studies on the bicyclomycinRho interaction. Biochemistry 39, 9067-9076.
46. Brogan, A. P., Widger, W. R., Bensadek, D., Riba-Garcia, I., Gaskell, S. J., Kohn, H. 2005, Development of a technique to determine bicyclomycin-rho binding and stoichiometry by isothermal titration calorimetry and mass spectrometry. J. Am. Chem. Soc. 127, 2741-2751.
47. Skordalakes, E., Brognan, A. P., Park, B. S., Kohn, H., Berger, J. M. 2005, Structural mechanism of inhibition of the Rho transcription termination factor by the antibiotic bicyclomycin. Structure 13, 99-109.
48. Banerjee, A. L., Eiler, D., Roy, B. C., Jia, X., Haldar, M. K., Mallik, S., Srivastava, D. K. 2005, Spacer-based selectivity in the binding of "two-prong" ligands to recombinant human carbonic anhydrase I. Biochemistry 44, 3211-3224.
49. Roy, B. C., Hegge, R., Rosendahl, T., Jia, X., Lareau, R., Mallik, S., Srivastava, D. K. 2003, Conjugation of poor inhibitors with surface binding groups: a strategy to improve inhibition. Chem. Commun. 2003, 2328-2329.
50. Banerjee, A. L., Swanson, M., Roy, B. C., Jia, X., Haldar, M. K., Mallik, S., Srivastava, D. K. 2004, Protein surface-assisted enhancement in the binding affinity of an inhibitor for recombinant human carbonic anhydrase-II. J. Am. Chem. Soc. 126, 10875-10883.
51. DeLano, W. L. 2004, PyMOL, available at: http://pymol.sourceforge.net/.