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Development of a FRET-based High-Throughput Screening System for the Discovery of Hsp90 Inhibitors

  • Oh, Sang-Mi (Department of Chemistry, Seoul National University) ;
  • Ko, Yeon-Jin (Department of Chemistry, Seoul National University) ;
  • Lee, Han-Jae (Department of Chemistry, Seoul National University) ;
  • Kim, Jong-Hoon (Department of Chemistry, Seoul National University) ;
  • Chung, Young-Sun (Department of Counseling, Korea Cyber University) ;
  • Park, Seung-Bum (Department of Chemistry, Seoul National University)
  • Received : 2011.06.30
  • Accepted : 2011.07.13
  • Published : 2011.09.20

Abstract

A FRET-based high-throughput screening system was developed for the discovery of competitive smallmolecule Hsp90 inhibitors. The biarsenical fluorescein derivative FlAsH and dabcyl-conjugated Hsp90 inhibitor GM were employed as the FRET donor and quencher, respectively. The spatial proximity perturbation between FlAsH-labeled Hsp90N and GM-dabcyl upon treatment of a small molecule led to changes in the FRET-induced fluorescence, monitored in a high-throughput fashion.

Keywords

References

  1. Young, J. C.; Moarefi, I.; Hartl, F. U. J. Cell Biol. 2001, 154, 267. https://doi.org/10.1083/jcb.200104079
  2. Whitesell, L.; Lindquist, S. L. Nat. Rev. Cancer 2005, 5, 761. https://doi.org/10.1038/nrc1716
  3. Sharp, S.; Workman, P. Adv. Cancer Res. 2006, 95, 323. https://doi.org/10.1016/S0065-230X(06)95009-X
  4. Neckers, L. J. Biosci. 2007, 32, 517. https://doi.org/10.1007/s12038-007-0051-y
  5. Chiosis, G.; Vilenchik, M.; Kim, J.; Solit, D. Drug Discov. Today 2004, 9, 881. https://doi.org/10.1016/S1359-6446(04)03245-3
  6. Calderwood, S. K.; Khaleque, M. A.; Sawyer, D. B.; Ciocca, D. R. Trends Biochem. Sci. 2006, 31, 164. https://doi.org/10.1016/j.tibs.2006.01.006
  7. Biamonte, M. A.; Van de Water, R.; Arndt, J. W.; Scannevin, R. H.; Perret, D.; Lee, W.-C. J. Med. Chem. 2010, 53, 3. https://doi.org/10.1021/jm9004708
  8. Stebbins, C. E.; Russo, A. A.; Schneider, C.; Rosen, N.; Hartl, F. U.; Pavletich, N. P. Cell 1997, 89, 239. https://doi.org/10.1016/S0092-8674(00)80203-2
  9. Roe, S. M.; Prodromou, C.; O'Brien, R.; Ladbury, J. E.; Piper, P. W.; Pearl, L. H. J. Med. Chem. 1999, 42, 260. https://doi.org/10.1021/jm980403y
  10. Neckers, L.; Schulte, T. W.; Mimnaugh, E. Invest. New Drugs 1999, 17, 361. https://doi.org/10.1023/A:1006382320697
  11. Kelland, L. R.; Sharp, S. Y.; Rogers, P. M.; Myers, T. G.; Workman, P. J. Natl. Cancer Inst. 1999, 91, 1940. https://doi.org/10.1093/jnci/91.22.1940
  12. Banerji, U.; Walton, M.; Raynaud, F.; Grimshaw, R.; Kelland, L.; Valenti, M.; Judson, I.; Workman, P. Clin. Cancer Res. 2005, 11, 7023. https://doi.org/10.1158/1078-0432.CCR-05-0518
  13. Solit, D. B.; Chiosis, G. Drug Discov. Today 2008, 13, 38. https://doi.org/10.1016/j.drudis.2007.10.007
  14. Chandarlapaty, S.; Sawai, A.; Ye, Q.; Scott, A.; Silinski, M.; Huang, K.; Fadden, P.; Partdrige, J.; Hall, S.; Steed, P.; Norton, L.; Rosen, N.; Solit, D. B. Clin. Cancer Res. 2008, 14, 240. https://doi.org/10.1158/1078-0432.CCR-07-1667
  15. Okawa, Y.; Hideshima, T.; Steed, P.; Vallet, S.; Hall, S.; Huang, K.; Rice, J.; Barabasz, A.; Foley, B.; Ikeda, H.; Raje, N.; Kiziltepe, T.; Yasui, H.; Enatsu, S.; Anderson, K. C. Blood 2009, 113, 846. https://doi.org/10.1182/blood-2008-04-151928
  16. Carreras, C. W.; Schirmer, A.; Zhong, Z.; Santi, D. V. Anal. Biochem. 2003, 317, 40. https://doi.org/10.1016/S0003-2697(03)00060-5
  17. Llauger-Bufi, L.; Felts, S. J.; Huezo, H.; Rosen, N.; Chiosis, G. Bioorg. Med. Chem. Lett. 2003, 13, 3975. https://doi.org/10.1016/j.bmcl.2003.08.065
  18. Zhou, V.; Han, S.; Brinker, A.; Klock, H.; Caldwell, J.; Gu, X. Anal. Biochem. 2004, 331, 349. https://doi.org/10.1016/j.ab.2004.04.011
  19. Avila, C.; Hadden, M. K.; Ma, Z.; Kornilayev, B. A.; Ye, Q.-Z.; Blagg, B. S. J. Bioorg. Med. Chem. Lett. 2006, 16, 3005. https://doi.org/10.1016/j.bmcl.2006.02.063
  20. Galam, L.; Hadden, M. K.; Ma, Z.; Ye, Q.-Z.; Yun, B.-G.; Blagg, B. S. J.; Matts, R. L. Bioorg. Med. Chem. 2007, 15, 1939. https://doi.org/10.1016/j.bmc.2007.01.004
  21. Clegg, R. M. Curr. Opin. Biotechnol. 1995, 6, 103. https://doi.org/10.1016/0958-1669(95)80016-6
  22. Selvin, P. R. Nat. Struct. Bio. 2000, 7, 730. https://doi.org/10.1038/78948
  23. Tsien, R. Y. Ann. Rev. Biochem. 1998, 67, 509. https://doi.org/10.1146/annurev.biochem.67.1.509
  24. Lippincott- Schwartz, J.; Patterson, G. H. Science 2003, 300, 87. https://doi.org/10.1126/science.1082520
  25. Griffin, B. A.; Adams, S. R.; Tsien, R. Y. Science 1998, 281, 269. https://doi.org/10.1126/science.281.5374.269
  26. Adams, S. R.; Campbell, R. E.; Gross, L. A.; Martin, B. R.; Walkup, G. K.; Yao, Y.; Llopis, J.; Tsien, R. Y. J. Am. Chem. Soc. 2002, 124, 6063. https://doi.org/10.1021/ja017687n
  27. Ko, S. K.; Jang, H. J.; Kim, E.; Park, S. B. Chem. Commun. 2006, 2962.
  28. An, H.; Eum, S.-J.; Koh, M.; Lee, S. K.; Park, S. B. J. Org. Chem. 2008, 73, 1752. https://doi.org/10.1021/jo702196f
  29. Kim, Y.; Kim, J.; Park, S. B. Org. Lett. 2009, 11, 5214. https://doi.org/10.1021/ol902147u
  30. Oh, S.; Jang, H. J.; Ko, S. K.; Ko, Y.; Park, S. B. J. Comb. Chem. 2010, 12, 548. https://doi.org/10.1021/cc100044w

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