Identification of selective inhibitors of uncharacterized enzymes by high-throughput screening with fluorescent activity-based probes

Nature Biotechnology

Volumn 27, Issue 4, 2009, Pages 387-394

  Bachovchin, Daniel A ^a   Brown, Steven J ^a   Rosen, Hugh ^a   Cravatt, Benjamin F ^a  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACTIVITY-BASED PROBES; COMPETITIVE ACTIVITIES; DETOXIFICATION ENZYMES; FLUORESCENCE POLARIZATIONS; FLUORESCENT PROBES; FUNCTIONAL ANNOTATIONS; HIGH SELECTIVITIES; HIGH-THROUGHPUT SCREENINGS; HYDROLASE; PROTEOMIC ASSAYS; PUBLIC LIBRARIES; SELECTIVE INHIBITORS; SMALL MOLECULES; SUBSTRATE-FREE;

ASSAYS; CATALYSTS; DETOXIFICATION; FLUORESCENCE; LIBRARIES; PROBES;

ENZYMES;

CEPHAELINE; DEHYDROEMETINE; ELECTROPHILE; EMETINE; ENZYME INHIBITOR; FLUORESCENT DYE; GLUTATHIONE TRANSFERASE; GLUTATHIONE TRANSFERASE O1; HYDROLASE; OMEPRAZOLE; RETINOBLASTOMA BINDING PROTEIN 9; RIFAMPICIN; TUBULOSINE; UNCLASSIFIED DRUG;

ARTICLE; CONTROLLED STUDY; ENZYME ACTIVE SITE; ENZYME ACTIVITY; ENZYME MECHANISM; FLUORESCENCE POLARIZATION; HIGH THROUGHPUT SCREENING; HUMAN; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEOMICS; STRUCTURE ACTIVITY RELATION;

ENZYME INHIBITORS; FLUORESCENT DYES; SPECTROMETRY, FLUORESCENCE;

EID: 64349085775     PISSN: 10870156     EISSN: 15461696     Source Type: Journal    
DOI: 10.1038/nbt.1531     Document Type: Article

References (50)

1. Inglese, J. et al. High-throughput screening assays for the identification of chemical probes. Nat. Chem. Biol. 3, 466-479 (2007).
2. Shelat, A.A. & Guy, R.K. Scaffold composition and biological relevance of screening libraries. Nat. Chem. Biol. 3, 442-446 (2007).
3. Ann, K. et ai. A novel mechanistic class of fatty acid amide hydrolase inhibitors with remarkable selectivity. Biochemistry 46, 13019-13030(2007).
4. Jo, E. et ai. SIPl-selective in vivo-active agonists from high-throughput screening: off-the-shelf chemical probes of receptor interactions, signaling, and fate. Chem. Biol. 12, 703-715 (2005).
5. Dolma, S., Lessnick, S.L., Hahn, W.C. & Stockwell, B.R. Identification of genotype-selective antitumor agents using synthetic lethal chemical screening in engineered human tumor cells. Cancer Cell 3, 285-296 (2003).
6. Galperin, M.Y. & Koonin, E.V. 'Conserved hypothetical' proteins: prioritization of targets for experimental study. Nucleic Acids Res. 32, 5452-5463 (2004).
7. Woitach, J.T., Zhang, M., Niu, C.H. & Thorgeirsson, S.S. A retinoblastoma-binding protein that affects cell-cycle control and confers transforming ability. Nat. Genet. 19, 371-374 (1998).
8. Rao, M. & Sockanathan, S. Transmembrane protein GDE2 induces motor neuron differentiation in vivo. Science309, 2212-2215 (2005).
9. Semba, S. et ai. Biological functions of mammalian NIT1, the counterpart of the invertebrate NITFHITrosetta stone protein, a possible tumor suppressor. J. Biol. Chem. 281, 28244-28253(2006).
10. Evans, MJ. & Cravatt, B.F. Mechanism-based profiling of enzyme families. Chem. Rev. 106, 3279-3301 (2006).
11. Cravatt, B.F., Wright, A.T. & Kozarich, J.W. Activity-based protein profiling: from enzyme chemistry to proteomic chemistry. Annu. Rev. Biochem. 77, 383-414 (2008).
12. Jessani, N., Liu, Y, Humphrey, M. & Cravatt, B.F. Enzyme activity profiles of the secreted and membrane proteomethat depict cancer invasiveness. Proc. Natl. Acad. Sci. USA 99, 10335-10340 (2002).
13. Jessani, N. et al. A streamlined platform for high-content functional proteomics of primary human specimens. Nat. Methods 2, 691-697 (2005).
14. Joyce, J.A. et al. Cathepsin cysteine proteases are effectors of invasive growth and angiogenesis during multistage tumorigenesis. Cancer Cell 5, 443-453 (2004).
15. Adam, G.C., Sorensen, EJ. & Cravatt, B.F. Proteomic profiling of mechanistically distinct enzyme classes using a common chemotype. Nat. Biotechnol. 20, 805-809 (2002).
16. Greenbaum, D.C. et al. A role for the protease falcipain 1 in host cell invasion by the human malaria parasite. Science 298, 2002-2006 (2002).
17. Blankman, J.L., Simon, G.S. & Cravatt, B.F. A comprehensive profile of brain enzymes that hydrolyze the endocannabinoid 2-Arachidonoylglycerol. Chem. Biol. 14, 1347-1356 (2007).
18. Barglow, K.T. & Cravatt, B.F. Substrate mimicry in an activity-based probe that targets the nitrilase family of enzymes. Angew. Chem. Int. Edn. Engl. 45, 7408-7411 (2006).
19. Leung, D., Hardouin, C, Boger, D.L. & Cravatt, B.F. Discovering potent and selective reversible inhibitors of enzymes in complex proteomes. Nat. Biotechnol. 21, 687-691 (2003).
20. Chiang, K.P., Niessen, S., Saghatelian, A. & Cravatt, B.F. An enzyme that regulates ether lipid signaling pathways in cancer annotated by multidimensional profiling. Chem. Biol. 13, 1041-1050 (2006).
21. Li, W., Blankman, J.L. & Cravatt, B.F. A functional proteomic strategy to discover inhibitors for uncharacterized hydrolases. J. Am. Chem. Soc. 129, 9594-9595 (2007).
22. wicki, J.C. Fluorescence polarization and anisotropy in high-throughput screening: perspectives and primer. J. Biomol. Screen. 5, 297-306 (2000).
23. Vorobiev, S.M. et al. Crystal structure of human retinoblastoma binding protein 9. Proteins 74, 526-529 (2008).
24. Patricelli, M.P., Giang, D.K., Stamp, L.M. & Burbaum, J.J. Direct visualization of serine hydrolase activities in complex proteome using fluorescent active site-directed probes. Proteomicsì, 1067-1071 (2001).
25. Liu, Y, Patricelli, M.P & Cravatt, B.F. Activity-based protein profiling: the serine hydrolases. Proc. Natl. Acad. Sci. USA 96, 14694-14699 (1999).
26. Hoover, H.S., Blankman, J.L., Niessen, S. & Cravatt, B.F. Selectivity of inhibitors of endocannabinoid biosynthesis evaluated by activity-based protein profiling. Bioorg. Med. Chem. Lett. 18, 5838-5841 (2008).
27. Saario, S.M. ef ai. Characterization of the sulfhydryl-sensitive site in the enzyme responsible for hydrolysis of 2-arachidonoyl-glycerol in rat cerebellar membranes. Chem. Biol. 12, 649-656 (2005).
28. Feng, B.Y., Shelat, A., Doman, T.N., Guy, R.K. & Shoichet, B.K. High-throughput assays for promiscuous inhibitors. Nat. Chem. Biol. 1, 146-148 (2005).
29. Feng, B.Y. et ai. A high-throughput screen for aggregation-based inhibition in a large compound library. J. Med. Chem. 50, 2385-2390 (2007).
30. Feng, B.Y. & Shoichet, B.K. A detergent-based assay for the detection of promiscuous inhibitors. Nat. Protoc. 1, 550-553 (2006).
31. Boon-Unge, K. et ai. Emetine regulates the alternative splicing of Bcl-x through a protein phosphatase 1-dependent mechanism. Chem. Biol. 14, 1386-1392 (2007).
32. Keiser, MJ. et ai. Relating protein pharmacology by ligand chemistry. Nat. Biotechnol. 25, 197-206 (2007).
33. Grollman, A.P. Structural basis for inhibition of protein synthesis by emetine and cycloheximide based on an analogy between ipecac alkaloids and glutarimide antibiotics. Proc. Nati. Acad. Sci. USA 56, 1867-1874 (1966).
34. Gupta, R.S. & Siminovitch, L. The molecular basis of emetine resistance in Chinese hamster ovary cells: alteration in the 40S ribosomal subunit. Cell 10, 61-66 (1977).
35. Monks, TJ. & Jones, D.C. The metabolism and toxicity of quinones, quinonimines, quinone methides, and quinone-thioethers. Curr. Drug Metab. 3, 425-438 (2002).
36. Hayes, J.D., Flanagan, J.U. & Jowsey, I.R. Glutathione transferases. Ann?. Rev. Pharmacol. Toxicol. 45, 51-88 (2005).
37. Yan, X.D., Pan, L.Y, Yuan, Y, Lang, J.H. & Mao, N. Identification of platinum-resistance associated proteins through proteomic analysis of human ovarian cancer cells and their platinum-resistant sublines. J. Proteome Res. 6, 772-780 (2007).
38. Board, P.G. et ai. Identification, characterization, and crystal structure of the omega class glutathione transferases. J. Biol. Chem. 275, 24798-24806 (2000).
39. Whitbread, A.K. et ai. Characterization of the omega class of glutathione transferases. Methods Enzymol. 401, 78-99 (2005).
40. Zhang, K. & Wong, K.P. Glutathione conjugation of chlorambucil: measurement and modulation by plant polyphenols. Biochem. J. 325, 417-422 (1997).
41. Adam, G.C., Sorensen, EJ. & Cravatt, B.F Trifunctional chemical probes for the consolidated detection and identification of enzyme activities from complex proteomes. Mol. Cell. Proteomics 1, 828-835 (2002).
42. Liu, S., Cerione, R.A. & Clardy, J. Structural basis for the guanine nucleotide-binding activity of tissue transglutaminase and its regulation of transamidation activity. Proc. Nati. Acad. Sci. USA 99, 2743-2747 (2002).
43. Board, P.G. et ai. S-(4-Nitrophenacyl)glutathione is a specific substrate for glutathione transferase omega 1-1. Anal. Biochem. 374, 25-30 (2008).
44. Torta, F, Usuelli, V., Malgaroli, A. & Bachi, A. Proteomic analysis of protein S-nitrosylation. Proteomics 8, 4484-4494 (2008).
45. Poole, L.B. & Nelson, KJ. Discovering mechanisms of signaling-mediated cysteine oxidation. Curr. Opin. Chem. Biol. 12, 18-24 (2008).
46. Vila, A. et ai. Identification of protein targets of 4-hydroxynonenal using click chemistry for ex vivo biotinylation of azido and alkynyl derivatives. Chem. Res. Toxicol. 21, 432-444 (2008).
47. Hafner, M. et ai. Inhibition of cytohesins by SecinH3 leads to hepatic insulin resistance. Nature 444, 941-944 (2006).
48. Antczak, C, Radu, C. & Djaballah, H. A profiling platform for the identification of selective metalloprotease inhibitors. J. Biomol. Screen. 13, 285-294 (2008).
49. Patricelli, M.P. et ai. Functional interrogation of the kinome using nucleotide acyl phosphates. Biochemistry 46, 350-358 (2007).
50. Chandonia, J.M. & Brenner, S.E. The impact of structural genomics: expectations and outcomes. Science, 311 347-351 (2006).