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Chemical kinomics: a powerful strategy for target deconvolution

  • Kim, Do-Hee (Life/Health Division, Korea Institute of Science and Technology) ;
  • Sim, Tae-Bo (Life/Health Division, Korea Institute of Science and Technology)
  • Received : 2010.11.05
  • Published : 2010.11.30
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Abstract

Kinomics is an emerging and promising approach for deciphering kinomes. Chemical kinomics is a discipline of chemical genomics that is also referred to as "chemogenomics", which is derived from chemistry and biology. Chemical kinomics has become a powerful approach to decipher complicated phosphorylation-based cellular signaling networks with the aid of small molecules that modulate kinase functions. Moreover, chemical kinomics has played a pivotal role in the field of kinase drug discovery as it enables identification of new molecular targets of small molecule kinase modulators and/or exploitation of novel functions of known kinases and has also provided novel chemical entities as hit/lead compounds. In this short review, contemporary chemical kinomics technologies such as activity-based protein profiling, T7 kinasetagged phages, kinobeads, three-hybrid systems, fluorescenttagged kinase binding assays, and chemical genomic profiling are discussed along with a novel allosteric Bcr-Abl kinase inhibitor (GNF-2/GNF-5) as a successful application of chemical kinomics approaches.

Keywords

References

  1. Bossemeyer, D. (1995) Protein kinases- structure and function. FEBS Lett. 369, 57-61. https://doi.org/10.1016/0014-5793(95)00580-3
  2. Fabbro, D. and Garcia-Echeverria, C. (2002) Targeting protein kinases in cancer therapy. Curr. Opin. Drug. Discov. Devel. 5, 701-712.
  3. Fabbro, D., Ruetz, S., Buchdunger, E., Cowan-Jacob, S. W., Fendrich, G., Liebetanz, J., Mestan, J., O'Reilly, T., Traxler, P., Chaudhuri, B., Fretz, H., Zimmermann, J., Meyer, T., Caravatti, G., Furet, P. and Manley, P. W. (2002) Protein kinases as targets for anticancer agents: from inhibitors to useful drugs. Pharmacol. Ther. 93, 79-98. https://doi.org/10.1016/S0163-7258(02)00179-1
  4. Kim, J. A. (2003) Targeted therapies for the treatment of cancer. Am. J. Surg. 186, 264-268. https://doi.org/10.1016/S0002-9610(03)00212-5
  5. Manning, G., Whyte, D. B., Martinez, R., Hunter, T. and Sudarsanam, S. (2002) The protein kinase complement of the human genome. Science 298, 1912-1934. https://doi.org/10.1126/science.1075762
  6. Zhang, J., Yang, P. L. and Gray, N. S. (2009) Targeting cancer with small molecule kinase inhibitors. Nat. Rev. Cancer 9, 28-39. https://doi.org/10.1038/nrc2559
  7. Cohen, P. (2002) Protein kinases- the major drug targets of the twenty-first century? Nat. Rev. Drug Discov. 1, 309-315. https://doi.org/10.1038/nrd773
  8. Jeffery, D. A. and Bogyo, M. (2003) Chemical proteomics and its application to drug discovery. Curr. Opin. Biotechnol. 14, 87-95. https://doi.org/10.1016/S0958-1669(02)00010-1
  9. Salemme, F. R. (2003) Chemical genomics as an emerging paradigm for postgenomic drug discovery. Pharmacogenomics 4, 257-267. https://doi.org/10.1517/phgs.4.3.257.22692
  10. Rix, U., Hantschel, O., Durnberger, G., Remsing Rix, L. L., Planyavsky, M., Fernbach, N. V., Kaupe, I., Bennett, K. L., Valent, P., Colinge, J., Kocher, T. and Superti-Furga, G. (2007) Chemical proteomic profiles of the BCR-ABL inhibitors imatinib, nilotinib, and dasatinib reveal novel kinase and nonkinase targets. Blood 110, 4055-4063. https://doi.org/10.1182/blood-2007-07-102061
  11. Li, J., Rix, U., Fang, B., Bai, Y., Edwards, A., Colinge, J., Bennett, K. L., Gao, J., Song, L., Eschrich, S., Superti-Furga, G., Koomen, J. and Haura, E. B. (2010) A chemical and phosphoproteomic characterization of dasatinib action in lung cancer. Nat. Chem. Biol. 6, 291-299. https://doi.org/10.1038/nchembio.332
  12. Hunter, T. (1995) Protein kinases and phosphatases: the yin and yang of protein phosphorylation and signaling. Cell 80, 225-236. https://doi.org/10.1016/0092-8674(95)90405-0
  13. Johnson, L. N. and Lewis, R. J. (2001) Structural basis for control by phosphorylation. Chem. Rev. 101, 2209-2242. https://doi.org/10.1021/cr000225s
  14. Ostman, A. and Bohmer, F. D. (2001) Regulation of receptor tyrosine kinase signaling by protein tyrosine phosphatases. Trends Cell Biol. 11, 258-266. https://doi.org/10.1016/S0962-8924(01)01990-0
  15. Richardson, C. J., Gao, Q., Mitsopoulous, C., Zvelebil, M., Pearl, L. H. and Pearl, F. M. (2009) MoKCa databasemutations of kinases in cancer. Nucleic. Acids. Res. 37, D824-831.
  16. Johnson, L. N., Noble, M. E. and Owen, D. J. (1996) Active and inactive protein kinases: structural basis for regulation. Cell 85, 149-158. https://doi.org/10.1016/S0092-8674(00)81092-2
  17. Scapin, G. (2002) Structural biology in drug design: selective protein kinase inhibitors. Drug Discov. Today 7, 601-611. https://doi.org/10.1016/S1359-6446(02)02290-0
  18. Grant, S. K. (2009) Therapeutic protein kinase inhibitors. Cell. Mol. Life Sci. 66, 1163-1177. https://doi.org/10.1007/s00018-008-8539-7
  19. Croston, G. E. (2002) Functional cell-based uHTS in chemical genomic drug discovery. Trends Biotechnol. 20, 110-115. https://doi.org/10.1016/S0167-7799(02)01906-6
  20. Graves, P. R. and Haystead, T. A. (2002) Molecular biologist's guide to proteomics. Microbiol. Mol. Biol. Rev. 66, 39-63 https://doi.org/10.1128/MMBR.66.1.39-63.2002
  21. Zheng, X. S., Chan, T. F. and Zhou, H. H. (2004) Genetic and genomic approaches to identify and study the targets of bioactive small molecules. Chem. Biol. 11, 609-618. https://doi.org/10.1016/j.chembiol.2003.08.011
  22. Cravatt, B. F., Wright, A. T. and Kozarich, J. W. (2008) Activity-based protein profiling: from enzyme chemistry to proteomic chemistry. Annu. Rev. Biochem. 77, 383-414. https://doi.org/10.1146/annurev.biochem.75.101304.124125
  23. Speers, A. E. and Cravatt, B. F. (2004) Chemical strategies for activity-based proteomics. Chembiochem 5, 41-47. https://doi.org/10.1002/cbic.200300721
  24. Patricelli, M. P., Szardenings, A. K., Liyanage, M., Nomanbhoy, T. K., Wu, M., Weissig, H., Aban, A., Chun, D., Tanner, S. and Kozarich, J. W. (2007) Functional interrogation of the kinome using nucleotide acyl phosphates. Biochemistry 46, 350-358. https://doi.org/10.1021/bi062142x
  25. Adam, G. C., Burbaum, J., Kozarich, J. W., Patricelli, M. P. and Cravatt, B. F. (2004) Mapping enzyme active sites in complex proteomes. J. Am. Chem. Soc. 126, 1363-1368. https://doi.org/10.1021/ja038441g
  26. Liu, Y., Jiang, N., Wu, J., Dai, W. and Rosenblum, J. S. (2007) Polo-like kinases inhibited by wortmannin. Labeling site and downstream effects. J. Biol. Chem. 282, 2505-2511. https://doi.org/10.1074/jbc.M609603200
  27. Liu, Y., Shreder, K. R., Gai, W., Corral, S., Ferris, D. K. and Rosenblum, J. S. (2005) Wortmannin, a widely used phosphoinositide 3-kinase inhibitor, also potently inhibits mammalian polo-like kinase. Chem. Biol. 12, 99-107. https://doi.org/10.1016/j.chembiol.2004.11.009
  28. Wymann, M. P., Bulgarelli-Leva, G., Zvelebil, M. J., Pirola, L., Vanhaesebroeck, B., Waterfield, M. D. and Panayotou, G. (1996) Wortmannin inactivates phosphoinositide 3-kinase by covalent modification of Lys-802, a residue involved in the phosphate transfer reaction. Mol. Cell. Biol. 16, 1722-1733. https://doi.org/10.1128/MCB.16.4.1722
  29. Wolf-Yadlin, A., Sevecka, M. and MacBeath, G. (2009) Dissecting protein function and signaling using protein microarrays. Curr. Opin. Chem. Biol. 13, 398-405. https://doi.org/10.1016/j.cbpa.2009.06.027
  30. Min, D. H. and Mrksich, M. (2004) Peptide arrays: towards routine implementation. Curr. Opin. Chem. Biol. 8, 554-558. https://doi.org/10.1016/j.cbpa.2004.08.007
  31. Reimer, U., Reineke, U. and Schneider-Mergener, J. (2002) Peptide arrays: from macro to micro. Curr. Opin. Biotechnol. 13, 315-320. https://doi.org/10.1016/S0958-1669(02)00339-7
  32. Schutkowski, M., Reineke, U. and Reimer, U. (2005) Peptide arrays for kinase profiling. Chembiochem 6, 513-521. https://doi.org/10.1002/cbic.200400314
  33. Hilhorst, R., Houkes, L., van den Berg, A. and Ruijtenbeek, R. (2009) Peptide microarrays for detailed, highthroughput substrate identification, kinetic characterization, and inhibition studies on protein kinase A. Anal. Biochem. 387, 150-161. https://doi.org/10.1016/j.ab.2009.01.022
  34. Houseman, B. T., Huh, J. H., Kron, S. J. and Mrksich, M. (2002) Peptide chips for the quantitative evaluation of protein kinase activity. Nat. Biotechnol. 20, 270-274. https://doi.org/10.1038/nbt0302-270
  35. Wang, Z. (2009) The peptide microarray-based assay for kinase functionality and inhibition study. Methods Mol. Biol. 570, 329-337. https://doi.org/10.1007/978-1-60327-394-7_18
  36. Li, T., Liu, D. and Wang, Z. (2009) Microarray-based Raman spectroscopic assay for kinase inhibition by gold nanoparticle probes. Biosens. Bioelectron. 24, 3335-3339. https://doi.org/10.1016/j.bios.2009.04.033
  37. Wang, Z., Levy, R., Fernig, D. G. and Brust, M. (2006) Kinase-catalyzed modification of gold nanoparticles: a new approach to colorimetric kinase activity screening. J. Am. Chem. Soc. 128, 2214-2215. https://doi.org/10.1021/ja058135y
  38. Smith, G. P. (1985) Filamentous fusion phage: novel expression vectors that display cloned antigens on the virion surface. Science 228, 1315-1317. https://doi.org/10.1126/science.4001944
  39. Fabian, M. A., Biggs, W. H., 3rd, Treiber, D. K., Atteridge, C. E., Azimioara, M. D., Benedetti, M. G., Carter, T. A., Ciceri, P., Edeen, P. T., Floyd, M., Ford, J. M., Galvin, M., Gerlach, J. L., Grotzfeld, R. M., Herrgard, S., Insko, D. E., Insko, M. A., Lai, A. G., Lelias, J. M., Mehta, S. A., Milanov, Z. V., Velasco, A. M., Wodicka, L. M., Patel, H. K., Zarrinkar, P. P. and Lockhart, D. J. (2005) A small molecule-kinase interaction map for clinical kinase inhibitors. Nat. Biotechnol. 23, 329-336. https://doi.org/10.1038/nbt1068
  40. Dunn, J. J. and Studier, F. W. (1983) Complete nucleotide sequence of bacteriophage T7 DNA and the locations of T7 genetic elements. J. Mol. Biol. 166, 477-535. https://doi.org/10.1016/S0022-2836(83)80282-4
  41. Son, M., Hayes, S. J. and Serwer, P. (1988) Concatemerization and packaging of bacteriophage T7 DNA in vitro: determination of the concatemers' length and appearance kinetics by use of rotating gel electrophoresis. Virology 162, 38-46. https://doi.org/10.1016/0042-6822(88)90392-3
  42. Griffin, J. D. (2005) Interaction maps for kinase inhibitors. Nat. Biotechnol. 23, 308-309. https://doi.org/10.1038/nbt0305-308
  43. Bantscheff, M., Eberhard, D., Abraham, Y., Bastuck, S., Boesche, M., Hobson, S., Mathieson, T., Perrin, J., Raida, M., Rau, C., Reader, V., Sweetman, G., Bauer, A., Bouwmeester, T., Hopf, C., Kruse, U., Neubauer, G., Ramsden, N., Rick, J., Kuster, B. and Drewes, G. (2007) Quantitative chemical proteomics reveals mechanisms of action of clinical ABL kinase inhibitors. Nat. Biotechnol. 25, 1035-1044. https://doi.org/10.1038/nbt1328
  44. Gygi, S. P., Rist, B., Gerber, S. A., Turecek, F., Gelb, M. H. and Aebersold, R. (1999) Quantitative analysis of complex protein mixtures using isotope-coded affinity tags. Nat. Biotechnol. 17, 994-999. https://doi.org/10.1038/13690
  45. Peters, E. C. and Gray, N. S. (2007) Chemical proteomics identifies unanticipated targets of clinical kinase inhibitors. ACS Chem. Biol. 2, 661-664. https://doi.org/10.1021/cb700203j
  46. Becker, F., Murthi, K., Smith, C., Come, J., Costa-Roldan, N., Kaufmann, C., Hanke, U., Degenhart, C., Baumann, S., Wallner, W., Huber, A., Dedier, S., Dill, S., Kinsman, D., Hediger, M., Bockovich, N., Meier-Ewert, S., Kluge, A. F. and Kley, N. (2004) A three-hybrid approach to scanning the proteome for targets of small molecule kinase inhibitors. Chem. Biol. 11, 211-223. https://doi.org/10.1016/S1074-5521(04)00029-8
  47. Abida, W. M., Carter, B. T., Althoff, E. A., Lin, H. and Cornish, V. W. (2002) Receptor-dependence of the transcription read-out in a small molecule three-hybrid system. Chembiochem 3, 887-895. https://doi.org/10.1002/1439-7633(20020902)3:9<887::AID-CBIC887>3.0.CO;2-F
  48. Gallagher, S. S., Miller, L. W. and Cornish, V. W. (2007) An orthogonal dexamethasone-trimethoprim yeast threehybrid system. Anal. Biochem. 363, 160-162. https://doi.org/10.1016/j.ab.2006.12.013
  49. Spencer, D. M., Wandless, T. J., Schreiber, S. L. and Crabtree, G. R. (1993) Controlling signal transduction with synthetic ligands. Science 262, 1019-1024. https://doi.org/10.1126/science.7694365
  50. Caligiuri, M., Molz, L., Liu, Q., Kaplan, F., Xu, J. P., Majeti, J. Z., Ramos-Kelsey, R., Murthi, K., Lievens, S., Tavernier, J. and Kley, N. (2006) MASPIT: three-hybrid trap for quantitative proteome fingerprinting of small moleculeprotein interactions in mammalian cells. Chem. Biol. 13, 711-722. https://doi.org/10.1016/j.chembiol.2006.05.008
  51. Jester, B. W., Cox, K. J., Gaj, A., Shomin, C. D., Porter, J. R. and Ghosh, I. (2010) A coiled-coil enabled split-luciferase three-hybrid system: applied toward profiling inhibitors of protein kinases. J. Am. Chem. Soc. 132, 11727-11735. https://doi.org/10.1021/ja104491h
  52. Okram, B., Nagle, A., Adrian, F. J., Lee, C., Ren, P., Wang, X., Sim, T., Xie, Y., Xia, G., Spraggon, G., Warmuth, M., Liu, Y. and Gray, N. S. (2006) A general strategy for creating "inactive-conformation" abl inhibitors. Chem. Biol. 13, 779-786. https://doi.org/10.1016/j.chembiol.2006.05.015
  53. Simard, J. R., Getlik, M., Grutter, C., Pawar, V., Wulfert, S., Rabiller, M. and Rauh, D. (2009) Development of a fluorescent-tagged kinase assay system for the detection and characterization of allosteric kinase inhibitors. J. Am. Chem. Soc. 131, 13286-13296. https://doi.org/10.1021/ja902010p
  54. de Lorimier, R. M., Smith, J. J., Dwyer, M. A., Looger, L. L., Sali, K. M., Paavola, C. D., Rizk, S. S., Sadigov, S., Conrad, D. W., Loew, L. and Hellinga, H. W. (2002) Construction of a fluorescent biosensor family. Protein Sci. 11, 2655-2675. https://doi.org/10.1110/ps.021860
  55. Torkamani, A., Kannan, N., Taylor, S. S. and Schork, N. J. (2008) Congenital disease SNPs target lineage specific structural elements in protein kinases. Proc. Natl. Acad. Sci. U.S.A. 105, 9011-9016. https://doi.org/10.1073/pnas.0802403105
  56. Simard, J. R., Kluter, S., Grutter, C., Getlik, M., Rabiller, M., Rode, H. B. and Rauh, D. (2009) A new screening assay for allosteric inhibitors of cSrc. Nat. Chem. Biol. 5, 394-396. https://doi.org/10.1038/nchembio.162
  57. Kung, C., Kenski, D. M., Dickerson, S. H., Howson, R. W., Kuyper, L. F., Madhani, H. D. and Shokat, K. M. (2005) Chemical genomic profiling to identify intracellular targets of a multiplex kinase inhibitor. Proc. Natl. Acad. Sci. U.S.A. 102, 3587-3592. https://doi.org/10.1073/pnas.0407170102
  58. Hunter, T. and Plowman, G. D. (1997) The protein kinases of budding yeast: six score and more. Trends Biochem. Sci. 22, 18-22.
  59. Bishop, A. C., Ubersax, J. A., Petsch, D. T., Matheos, D. P., Gray, N. S., Blethrow, J., Shimizu, E., Tsien, J. Z., Schultz, P. G., Rose, M. D., Wood, J. L., Morgan, D. O. and Shokat, K. M. (2000) A chemical switch for inhibitor-sensitive alleles of any protein kinase. Nature 407, 395-401. https://doi.org/10.1038/35030148
  60. Nagar, B., Hantschel, O., Seeliger, M., Davies, J. M., Weis, W. I., Superti-Furga, G. and Kuriyan, J. (2006) Organization of the SH3-SH2 unit in active and inactive forms of the c-Abl tyrosine kinase. Mol. Cell. 21, 787-798. https://doi.org/10.1016/j.molcel.2006.01.035
  61. Schindler, T., Bornmann, W., Pellicena, P., Miller, W. T., Clarkson, B. and Kuriyan, J. (2000) Structural mechanism for STI-571 inhibition of abelson tyrosine kinase. Science 289, 1938-1942. https://doi.org/10.1126/science.289.5486.1938
  62. Cowan-Jacob, S. W., Guez, V., Fendrich, G., Griffin, J. D., Fabbro, D., Furet, P., Liebetanz, J., Mestan, J. and Manley, P. W. (2004) Imatinib (STI571) resistance in chronic myelogenous leukemia: molecular basis of the underlying mechanisms and potential strategies for treatment. Mini Rev. Med. Chem. 4, 285-299. https://doi.org/10.2174/1389557043487321
  63. Gorre, M. E., Mohammed, M., Ellwood, K., Hsu, N., Paquette, R., Rao, P. N. and Sawyers, C. L. (2001) Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science 293, 876-880. https://doi.org/10.1126/science.1062538
  64. von Bubnoff, N., Schneller, F., Peschel, C. and Duyster, J. (2002) BCR-ABL gene mutations in relation to clinical resistance of Philadelphia-chromosome-positive leukaemia to STI571: a prospective study. Lancet 359, 487-491. https://doi.org/10.1016/S0140-6736(02)07679-1
  65. Wong, S. and Witte, O. N. (2004) The BCR-ABL story: bench to bedside and back. Annu. Rev. Immunol. 22, 247-306. https://doi.org/10.1146/annurev.immunol.22.012703.104753
  66. Adrian, F. J., Ding, Q., Sim, T., Velentza, A., Sloan, C., Liu, Y., Zhang, G., Hur, W., Ding, S., Manley, P., Mestan, J., Fabbro, D. and Gray, N. S. (2006) Allosteric inhibitors of Bcr-abl-dependent cell proliferation. Nat. Chem. Biol. 2, 95-102. https://doi.org/10.1038/nchembio760
  67. Zhang, J., Adrian, F. J., Jahnke, W., Cowan-Jacob, S. W., Li, A. G., Iacob, R. E., Sim, T., Powers, J., Dierks, C., Sun, F., Guo, G. R., Ding, Q., Okram, B., Choi, Y., Wojciechowski, A., Deng, X., Liu, G., Fendrich, G., Strauss, A., Vajpai, N., Grzesiek, S., Tuntland, T., Liu, Y., Bursulaya, B., Azam, M., Manley, P. W., Engen, J. R., Daley, G. Q., Warmuth, M. and Gray, N. S. (2010) Targeting Bcr-Abl by combining allosteric with ATP-binding-site inhibitors. Nature 463, 501-506. https://doi.org/10.1038/nature08675
  68. Wales, T. E. and Engen, J. R. (2006) Hydrogen exchange mass spectrometry for the analysis of protein dynamics. Mass Spectrom. Rev. 25, 158-170. https://doi.org/10.1002/mas.20064

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