Small-molecule affinity chromatography coupled mass spectrometry for drug target deconvolution

Expert Opinion on Drug Discovery

Volumn 4, Issue 7, 2009, Pages 701-714

  Saxena, Chaitanya ^a   Higgs, Richard E ^a   Zhen, Eugene ^a   Hale, John E ^a  

^a ELI LILLY AND COMPANY   (United States)

Author keywords

Chemical proteomics; Chemo proteomics; Immuno chemo proteomics; Mass spectrometry; Peptide coupled small molecule; Small molecule affinity chromatography; Target deconvolution; Target identification

Indexed keywords

4 (4 FLUOROPHENYL) 2 (4 HYDROXYPHENYL) 5 (4 PYRIDYL)IMIDAZOLE; AMPICILLIN; BISINDOLYLMALEIMIDE; BOSUTINIB; CALMODULIN INHIBITOR; CARBOXYLIC ACID DERIVATIVE; D 492; DASATINIB; DEXAMETHASONE; FENOFIBRATE; HBC; IMATINIB; INDISULAM; QUINOLINE; ROSCOVITINE; TACROLIMUS; TARENFLURBIL; UNCLASSIFIED DRUG;

AFFINITY CHROMATOGRAPHY; CHRONIC MYELOID LEUKEMIA; DNA LIBRARY; DRUG DESIGN; DRUG MECHANISM; DRUG PROTEIN BINDING; DRUG SCREENING; DRUG SELECTIVITY; DRUG TARGETING; FRACTIONATION; HUMAN; ISOTOPE LABELING; MASS SPECTROMETRY; MICROARRAY ANALYSIS; NONHUMAN; PHAGE DISPLAY; PHENOTYPE; PHOTOAFFINITY LABELING; PRIORITY JOURNAL; PROTEIN CONTENT; PROTEIN DETERMINATION; PROTEIN TARGETING; REPRODUCIBILITY; REVIEW; TOXICITY TESTING; YEAST;

EID: 67650708399     PISSN: 17460441     EISSN: None     Source Type: Journal    
DOI: 10.1517/17460440903005565     Document Type: Review

References (69)

1. Imming P, Sinning C, Meyer A. Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov 2006;5:821-834 (Pubitemid 44480536)
2. Hale JE, Ou W, Shiyanov P, et al. Proteomics technologies for identification and validation of protein targets. In: Figeys D, Ross MM (Eds), Industrial Proteomics: Applications for Biotechnology and Pharmaceuticals. J Wiley & Sons, Inc., Hoboken, NJ, USA; 2005. p. 159-80 ••This review describes various available proteomics technologies including mass spectrometry based methods for target identification and validation.
3. Saxena C, Zhen E, Higgs RE, Hale JE. An immuno-chemo-proteomics method for drug target deconvolution. J Proteome Res 2008;7:3490-3497 ••This article describes the development of soluble probe, a peptide-coupled small-molecule method for target identification, where antibody against the peptide was used to affinity isolate the small-molecule-target protein complex.
4. Terstappen GC, Schlüpen C, Raggiaschi R, Gaviraghi G. Target deconvolution strategies in drug discovery. Nat Rev Drug Discov 2007;6:891-903 ••This review describes various available methods for target deconvolution including affinity chromatography, expression cloning, biochemical suppression and micro-array technologies. (Pubitemid 350042397)
5. Sams-Dodd F. Target-based drug discovery: is something wrong? Drug Discov Today 2005;10:139-147
6. Bharucha N, Kumar A. Yeast genomics and drug target identification. Comb Chem High Throughput Screen 2007;10:618-634 (Pubitemid 350099309)
7. Wang Y, Chiu JF, He QY. Proteomics approach to illustrate drug action mechanisms. Curr Drug Discov Technol 2006;3:199-209 (Pubitemid 46425956)
8. Hart CP. Finding the target after screening the phenotype. Drug Discov Today 2005;10:513-519
9. Wang S, Sim TB, Kim YS, Chang YT. Tools for target identification and validation. Curr Opin Chem Biol 2004;8:371-377
10. Kassner PD. Discovery of novel targets with high throughput RNA interference screening. Comb Chem High Throughput Screen 2008;11:175-184 •This article describes RNAi based screen approaches for new target identification, a critical method that is not presented in the current review.
11. Loo JA, DeJohn DE, Du P, et al. Application of mass spectrometry for target identification and characterization. Med Res Rev 1999;19:307-319
12. Deng G, Sanyal G. Applications of mass spectrometry in early stages of target based drug discovery. J Pharm Biomed Anal 2006;40:528-538 (Pubitemid 43227375)
13. Glish GL, Vachet RW. The basics of mass spectrometry in the twenty-first century. Nat Rev Drug Discov 2003;2:140-150 (Pubitemid 37361646)
14. Peterson JR, Lebensohn AM, Pelish HE, Kirschner MW. Biochemical suppression of small-molecule inhibitors: a strategy to identify inhibitor targets and signaling pathway components. Chem Biol 2006;13:443-452
15. Lee JC, Laydon JT, McDonnell PC, et al. A protein kinase involved in the regulation of inflammatory cytokine biosynthesis. Nature 1994;372:739-746
16. Eriksen JL, Sagi SA, Smith TE, et al. NSAIDs and enantiomers of flurbiprofen target gamma-secretase and lower Aβ 42 in vivo. J Clin Invest 2003;112:440-449 (Pubitemid 38063773)
17. Kukar T, Prescott S, Eriksen JL, et al. Chronic administration of R-flurbiprofen attenuates learning impairments in transgenic amyloid precursor protein mice. BMC Neurosci 2007;8:54
18. Wolfe MS. γ-Secretase modulators. Curr Alzheimer Res 2007;4:571-573
19. Kukar TL, Ladd TB, Bann MA, et al. Substrate-targeting γ-secretase modulators. Nature 2008;453:925-930
20. Shim JS, Lee J, Park HJ, et al. A new curcumin derivative, HBC, interferes with the cell cycle progression of colon cancer cells via antagonization of the Ca2 + /calmodulin function. Chem Biol 2004;11:1455-1463
21. Licitra EJ, Liu JO. A three-hybrid system for detecting small ligand-protein receptor interactions. Proc Natl Acad Sci USA 1996;93:12817-21 •This article is the first account that three-hybrid system (evolving from yeast two-hybrid system) can be successfully used in target identification.
22. Henthorn DC, Jaxa-Chamiec AA, Meldrum E. A GAL4-based yeast three-hybrid system for the identification of small molecule-target protein interactions. Biochem Pharmacol 2002;63:1619-1628 (Pubitemid 34458001)
23. Lin H, Abida WM, Sauer RT, et al. Dexamethasone-Methotrexate: an efficient chemical inducer of protein dimerization in vivo. J Am Chem Soc 2000;122:4247-4248 (Pubitemid 30304874)
24. Becker F, Murthi K, Smith C. A three-hybrid approach to scanning the proteome for targets of small molecule kinase inhibitors. Chem Biol 2004;11:211-223 (Pubitemid 38300291)
25. Sun H, Chattopadhaya S, Wang J, Yao SQ. Recent developments in microarray-based enzyme assays: from functional annotation to substrate/inhibitor fingerprinting. Anal Bioanal Chem 2006;386:416-426 (Pubitemid 44450923)
26. Bertone P, Snyder M. Advances in functional protein microarray technology. FEBS Journal 2005;272:5400-5411 (Pubitemid 41579404)
27. Huang J, Zhu H, Haggarty SJ, et al. Finding new components of the target of rapamycin (TOR) signaling network through chemical genetics and proteome chips. Proc Natl Acad Sci USA 2004;101:16594-16599
28. Ziauddin J, Sabatini DM. Microarrays of cells expressing defined cDNAs. Nature 2001;411:107-110 (Pubitemid 32428199)
29. Brissette R, Prendergast JK, Goldstein NI. Identification of cancer targets and therapeutics using phage display. Curr Opin Drug Discov Devel 2006;9:363-439
30. Caligiuri M, Molz L, Liu Q, et al. MASPIT: three-hybrid trap for quantitative proteome fingerprinting of small molecule-protein interactions in mammalian cells. Chem Biol 2006;13:711-722
31. Stoll D, Templin MF, Bachmann J, Joos TO. Protein microarrays: applications and future challenges. Curr Opin Drug Discov Devel 2005;8:239-252 (Pubitemid 40348975)
32. Karas M, Hillenkamp F. Laser desorption ionization of proteins with molecular masses exceeding 10,000 daltons. Anal Chem 1988;60:2299-2301
33. Fenn JB, Mann M, Meng CK, et al. Electrospray ionization for mass spectrometry of large biomolecules. Science 1989;246:64-71
34. Cottrell JS. Protein identification by peptide mass fingerprinting. Pept Res 1994;7:115-124 (Pubitemid 2109897)
35. Dass C. Principles and Practices of Biological Mass Spectrometry. Wiley-Interscience, 2001 ••A comprehensive resource book for fundamentals of biological mass spectrometry; a newer version 2007 is available now.
36. Gygi SP, Rist B, Gerber SA, et al. Quantitative analysis of complex protein mixturesusing isotope-coded affinity tags. Nat Biotechnol 1999;17:994-999
37. Krause E, Wenschcuh H, Jungblut PR. The dominance of arginine-containing peptides in MALDI-derived tryptic mass fingerprints of proteins. Anal Chem 1999;71:4160-4165 (Pubitemid 29466391)
38. Oda Y, Huang K, Croos FR, et al. Accurate quantitation of protein expression and site specific phosphorylation. Proc Natl Acad Sci USA 1999;96:6591-6596
39. Mirgorodskaya OA, Kozmin YP, Titov MI, et al. Quantitation of peptides and proteins by matrix-assisted laser desorption/ionisation mass spectrometry using 18O-labeled internal standards. Rapid Commun Mass Spectrom 2000;14:1226-1232
40. Yao X, Freas A, Ramirez J, et al. Proteolytic 18O labeling for comparative proteomics: Model studies with two serotypes of adenovirus. Anal Chem 2001;73:2836-2842
41. Goodlett DR, Keller A, Watts JD, et al. Differential stable isotope labeling of peptides for quantitation and de novo sequence derivation. Rapid Commun Mass Spectrom 2001;15:1214-1221
42. Ong S-E, Blagoev B, Kratchmarova I, et al. Stable isotop labeling by amino acids in cell culture, SILAC, as a simple and accurate approach to expression proteomics. Mol Cell Proteomics 2002;1:376-386
43. Chakraborty A, Regnier F. Global internal standard technology for comparative proteomics. J Chromatogr A 2002;949:173-184 (Pubitemid 34183425)
44. Wang S, Zhang X, Regnier FE. Quantitative proteomics strategy involving the selection of peptides containing both cysteine and histidine from tryptic digests of cell lysates. J Chromatogr A 2002;949:153-162 (Pubitemid 34183423)
45. Zhang R, Regnier FE. Controlling deuterium isotop effects in comparative proteomics. Anal Chem 2002;74:3662-3669 (Pubitemid 34855856)
46. Bondarenko PV, Chelius D, Shaler TA. Identification and relative quantitation of protein mixtures by enzymatic digestion followed by capillary reversed-phase liquid chromatography-tandem mass spectrometry. Anal Chem 2002;74:4741-4749 (Pubitemid 35051732)
47. Higgs RE, Knierman MD, Gelfanova V, et al. Comprehensive label-free method for the relative quantification of proteins from biological samples. J Proteome Res 2005;4:1441-1450
48. Hamdan M, Righetti PG. Modern strategies for protein quantification in proteome analysis: advantages and limitations. Mass Spectrom Rev 2002;21:287-302
49. Pütz S, Reinders J, Reinders Y, Sickmann A. Mass spectrometry-based peptide quantification: applications and limitations. Expert Rev Proteomics 2005;2:381-392 (Pubitemid 40839748)
50. Kiernan UA. Quantitation of target proteins and post-translational modifications in affinity-based proteomics approaches. Expert Rev Proteomics 2007;4:421-428 (Pubitemid 46890079)
51. Bach S, Knockaert M, Reinhardt J, et al. Roscovitine Targets, Protein Kinases and Pyridoxal Kinase. J Biol Chem 2005;280:31208-31219 (Pubitemid 41291858)
52. Snyder J, Hall A, Ni-Komatsu L, et al. Dissection of Melanogenesis with Small Molecules Identifies Prohibitin as a Regulator. Chem Biol 2005;12:477-484
53. Hantschel O, Rix U, Schmidt U, et al. The Btk tyrosine kinase is a major target of the Bcr-Abl inhibitor dasatinib. Proc Natl Acad Sci USA 2007;104:13282-13288
54. Remsing Rix LL, Rix U, Colinge J, et al. Global target profile of the kinase inhibitor bosutinib in primary chronic myeloid leukemia cells. Leukemia 2009;23:477-485
55. Bantscheff M, Eberhard D, Abraham Y, et al. Quantitative chemical proteomics reveals mechanisms of action of clinical ABL kinase inhibitors. Nat Biotechnol 2007;25:1035-44 ••Describes the use of quantitative mass spectrometry in conjunction with the small-molecule affinity chromatography to deconvolute kinase and purine binding targets of small-molecule kinase inhibitors. Although study remains limited with the capture of kinase and purine binding proteins only, this elegant study is one of the best examples of small-molecule affinity chromatography coupled mass spectrometry based methods for target deconvolution.
56. Godl K, Wissing J, Kurtenbach A, et al. An efficient proteomics method to identify the cellular targets of protein kinase inhibitors. Proc Natl Acad Sci USA 2007;100:15434-15439
57. Hahn R, Berger E, Pflegerl K, et al. Directed immobilization of peptide ligands to accessible pore sites by conjugation with a placeholder molecule. Anal Chem 2003;75:543-548
58. Graves PR, Kwiek JJ, Fadden P, et al. Discovery of novel targets of quinoline drugs in the human purine binding proteome. Mol Pharmacol 2002;62:1364-1372
59. Hall SE. Chemoproteomics-driven drug discovery: addressing high attrition rates. Drug Discov Today 2006;11:495-502
60. Bertinetti D, Schweinsberg S, Hanke SE, et al. Chemical tools selectively target components of the PKA system. BMC Chem Biol 2009;9:3
61. von Rechenberg M, Blake BK, Ho YS, et al. Ampicillin/penicillin-binding protein interactions as a model drug-target system to optimize affinity pull-down and mass spectrometric strategies for target and pathway identification. Proteomics 2005;5:1764-1773
62. Sato S, Kwon Y, Kamisuki S, et al. Polyproline-rod approach to isolating protein targets of bioactive small molecules: isolation of a new target of indomethacin. J Am Chem Soc 2007;129:873-880 (Pubitemid 46188236)
63. Kosaka T, Okuyama R, Sun W, et al. Identification of molecular target of AMP-activated protein kinase activator by affinity purification and mass spectrometry. Anal Chem 2005;77:2050-2055
64. Oda Y, Owa T, Sato T, et al. Quantitative chemical proteomics for identifying candidate drug targets. Anal Chem 2003;75:2159-65 ••A systematic strategy including the use of a negative affinity matrix and the covalent labeling of the proteins with cleavable isotope-coded affinity tag (ICAT) was developed to identifying the targets.
65. Ong SE, Schenone M, Margolin AA, et al. Identifying the proteins to which small-molecule probes and durgs bind in cells. Proc Natl Acad Sci USA 2009 [Epub ahead of print] •• Utilizes a quantitative proteomics techniques to specify the target interaction with small-molecules in affinity chromatographic experiments.
66. Käll L, Storey JD, Maccoss MJ, Noble WS. Assigning significance to peptides identified by tandem mass spectrometry using decoy databases. J Proteome Res 2008;7:29-34 (Pubitemid 351171110)
67. Käll L, Canterbury JD, Weston J, et al. Semi-supervised learning for peptide identification from shotgun proteomics datasets. Nat Meth 2007;4:923-925
68. Sleno L, Emili A. Proteomic methods for drug target discovery. Curr Opin Chem Biol 2008;12:46-54
69. Bumol TF, Watanabe AM. Genetic information, genomic technologies, and the future of drug discovery. JAMA 2001;285:551-555 (Pubitemid 32656322)