Advertisement

Probing Biology with Small Molecule Microarrays (SMM)

  • Nicolas WinssingerEmail author
  • Zbigniew Pianowski
  • Francois Debaene
Chapter
Part of the Topics in Current Chemistry book series (TOPCURRCHEM, volume 278)

Abstract

In the continuous drive to increase screening throughput and reduce sample requirement, microarray-based technologies have risen to the occasion. In the past 7 years, a number of new methodologies have been developed for preparing small molecule microarrays from combinatorial and natural product libraries with the goal of identifying new interactions or enzymatic activities. Recent advances and applications of small molecule microarrays are reviewed.

Activity profiling Combinatorial libraries Diagnostic Screening Small molecule microarray (SMM) 

References

  1. 1.
    Heller MJ (2002) DNA microarray technology: devices, systems, and applications. Ann Rev Biomed Eng 4:129–153 CrossRefGoogle Scholar
  2. 2.
    Pirrung MC (2002) How to make a DNA chip. Angew Chem Int Ed 41:1276–1289 CrossRefGoogle Scholar
  3. 3.
    Brown P (2004) The MGuide. Version 2.0. http://www.cmgm.stanford.edu/pbrown/mguide/index.html (last visited: 26 Jan 2007)
  4. 4.
    Conzone SD, Pantano CG (2004) Glass slides to DNA microarrays. Mater Today 7:20–26 CrossRefGoogle Scholar
  5. 5.
    Bradner JE et al. (2006) A robust small-molecule microarray platform for screening cell lysates. Chem Biol 13:493–504 CrossRefGoogle Scholar
  6. 6.
    Lee MR, Shin I (2005) Fabrication of chemical microarrays by efficient immobilization of hydrazide-linked substances on epoxide-coated glass surfaces. Angew Chem Int Ed 44:2881–2884 CrossRefGoogle Scholar
  7. 7.
    Kanoh N et al. (2003) Immobilization of natural products on glass slides by using a photoaffinity reaction and the detection of protein-small-molecule interactions. Angew Chem Int Ed 42:5584–5587 CrossRefGoogle Scholar
  8. 8.
    Hergenrother PJ, Depew KM, Schreiber SL (2000) Small-molecule microarrays: covalent attachment and screening of alcohol-containing small molecules on glass slides. J Am Chem Soc 122:7849–7850 CrossRefGoogle Scholar
  9. 9.
    Falsey JR, Renil M, Park S, Li S, Lam KS (2001) Peptide and small molecule microarray for high throughput cell adhesion and functional assays. Bioconjugate Chem 12:346–353 CrossRefGoogle Scholar
  10. 10.
    Shin I, Park S, Lee MR (2005) Carbohydrate microarrays: an advanced technology for functional studies of glycans. Chemistry 11:2894–2901 CrossRefGoogle Scholar
  11. 11.
    Benters R, Niemeyer CM, Wohrle D (2001) Dendrimer-activated solid supports for nucleic acid and protein microarrays. ChemBioChem 2:686–694 CrossRefGoogle Scholar
  12. 12.
    Hackler L Jr et al. (2003) Development of chemically modified glass surfaces for nucleic acid, protein and small molecule microarrays. Mol Divers 7:25–36 CrossRefGoogle Scholar
  13. 13.
    Houseman BT, Huh JH, Kron SJ, Mrksich M (2002) Peptide chips for the quantitative evaluation of protein kinase activity. Nat Biotechnol 20:270–274 CrossRefGoogle Scholar
  14. 14.
    Lee K-B, Park S-J, Mirkin CA, Smith JC, Mrksich M (2002) Protein nanoarrays generated by dip-pen nanolithography. Science 295:1702–1705 CrossRefGoogle Scholar
  15. 15.
    Lee SW et al. (2006) Biologically active protein nanoarrays generated using parallel dip-pen nanolithography. Adv Mater 18:1133–1136 CrossRefGoogle Scholar
  16. 16.
    Fodor SPA et al. (1991) Light-directed, spatially addressable parallel chemical synthesis. Science 251:767–773 CrossRefGoogle Scholar
  17. 17.
    Cho CY et al. (1993) An unnatural biopolymer. Science 261:1303–1305 CrossRefGoogle Scholar
  18. 18.
    Pease AC et al. (1994) Light-generated oligonucleotide arrays for rapid DNA sequence analysis. Proc Natl Acad Sci USA 91:5022–5026 CrossRefGoogle Scholar
  19. 19.
    McGall G et al. (1996) Light-directed synthesis of high-density oligonucleotide arrays using semiconductor photoresists. Proc Natl Acad Sci USA 93:13555–13560 CrossRefGoogle Scholar
  20. 20.
    Singh-Gasson S et al. (1999) Maskless fabrication of light-directed oligonucleotide microarrays using a digital micromirror array. Nat Biotechnol 17:974–978 CrossRefGoogle Scholar
  21. 21.
    Li S et al. (2004) Photolithographic synthesis of peptoids. J Am Chem Soc 126:4088–4089 CrossRefGoogle Scholar
  22. 22.
    Li S, Marthandan N, Bowerman D, Garner HR, Kodadek T (2005) Photolithographic synthesis of cyclic peptide arrays using a differential deprotection strategy. Chem Comm pp 581–583 Google Scholar
  23. 23.
    LeProust E et al. (2000) Digital light-directed synthesis. A microarray platform that permits rapid reaction optimization on a combinatorial basis. J Comb Chem 2:49–354 CrossRefGoogle Scholar
  24. 24.
    Pellois JP, Wang W, Gao X (2000) Peptide synthesis based on t-Boc chemistry and solution photogenerated acids. J Comb Chem 2:355–360 CrossRefGoogle Scholar
  25. 25.
    Pellois JP et al. (2002) Individually addressable parallel peptide synthesis on microchips. Nat Biotechnol 20:922–926 CrossRefGoogle Scholar
  26. 26.
    Frank R, Gueler S, Krause S, Lindenmaier W (1991) Facile and rapid spot-synthesis of large numbers of peptides on membrane sheets. Pept 1990, Proc 21st Eur Pept Symp, pp 151–152 Google Scholar
  27. 27.
    Frank R (1992) Spot-synthesis: an easy technique for the positionally addressable, parallel chemical synthesis on a membrane support. Tetrahedron 48:9217–9232 CrossRefGoogle Scholar
  28. 28.
    Frank R (2002) The SPOT-synthesis technique. Synthetic peptide arrays on membrane supports–principles and applications. J Immunol Methods 267:13–26 CrossRefGoogle Scholar
  29. 29.
    Scharn D, Wenschuh H, Reineke U, Schneider-Mergener J, Germeroth L (2000) Spatially addressed synthesis of amino- and amino-oxy-substituted 1,3,5-triazine arrays on polymeric membranes. J Comb Chem 2:361–369 CrossRefGoogle Scholar
  30. 30.
    Scharn D, Germeroth L, Schneider-Mergener J, Wenschuh H (2001) Sequential nucleophilic substitution on halogenated triazines, pyrimidines, and purines: a novel approach to cyclic peptidomimetics. J Org Chem 66:507–513 CrossRefGoogle Scholar
  31. 31.
    Heine N, Germeroth L, Schneider-Mergener J, Wenschuh H (2001) A modular approach to the SPOT-synthesis of 1,3,5-trisubstituted hydantoins on cellulose membranes. Tetrahedron Lett 42:227–230 CrossRefGoogle Scholar
  32. 32.
    Niggemann J, Michaelis K, Frank R, Zander N, Hoefle G (2002) Natural product-derived building blocks for combinatorial synthesis. Part 1. Fragmentation of natural products from myxobacteria. J Chem Soc. Perkin Trans 1, pp 2490–2503 Google Scholar
  33. 33.
    Bowman Matthew D, Jeske Ryan C, Blackwell Helen E (2004) Microwave-accelerated SPOT-synthesis on cellulose supports. Org Lett 6:2019–2022 CrossRefGoogle Scholar
  34. 34.
    Lin Q, O'Neill JC, Blackwell HE (2005) Small molecule macroarray construction via Ugi four-component reactions. Org Lett 7:4455–4458 CrossRefGoogle Scholar
  35. 35.
    MacBeath G, Koehler AN, Schreiber SL (1999) Printing small molecules as microarrays and detecting protein–ligand interactions en masse. J Am Chem Soc 121:7967–7968 CrossRefGoogle Scholar
  36. 36.
    Kuruvilla FG, Shamji AF, Sternson SM, Hergenrother PJ, Schreiber SL (2002) Dissecting glucose signalling with diversity-oriented synthesis and small-molecule microarrays. Nature 416:653–657 CrossRefGoogle Scholar
  37. 37.
    Melnyk O et al. (2002) Peptide arrays for highly sensitive and specific antibody-binding fluorescence assays. Bioconjugate Chem 13:713–720 CrossRefGoogle Scholar
  38. 38.
    de Araujo AD et al. (2005) Diels–Alder ligation and surface immobilization of proteins. Angew Chem Int Ed 45:296–301 CrossRefGoogle Scholar
  39. 39.
    Barnes-Seeman D, Park SB, Koehler AN, Schreiber SL (2003) Expanding the functional group compatibility of small-molecule microarrays: discovery of novel calmodulin ligands. Angew Chem Int Ed 42:2376–2379 CrossRefGoogle Scholar
  40. 40.
    Nilsson BL, Kiessling LL, Raines RT (2000) Staudinger ligation: a peptide from a thioester and azide. Org Lett 2:1939–1941 CrossRefGoogle Scholar
  41. 41.
    Saxon E, Armstrong JI, Bertozzi CR (2000) A traceless Staudinger ligation for the chemoselective synthesis of amide bonds. Org Lett 2:2141–2143 CrossRefGoogle Scholar
  42. 42.
    Soellner MB, Dickson KA, Nilsson BL, Raines RT (2003) Site-specific protein immobilization by Staudinger ligation. J Am Chem Soc 125:11790–11791 CrossRefGoogle Scholar
  43. 43.
    Watzke A et al. (2006) Site-selective protein immobilization by staudinger ligation. Angew Chem Int Ed 45:1408–1412 CrossRefGoogle Scholar
  44. 44.
    Rostovtsev VV, Green LG, Fokin VV, Sharpless KB (2002) A stepwise Huisgen cycloaddition process: copper(I)-catalyzed regioselective ligation of azides and terminal alkynes. Angew Chem Int Ed 41:2596–2599 CrossRefGoogle Scholar
  45. 45.
    Bryan MC et al. (2004) Covalent display of oligosaccharide arrays in microtiter plates. J Am Chem Soc 126:8640–8641 CrossRefGoogle Scholar
  46. 46.
    Calarese DA et al. (2005) Dissection of the carbohydrate specificity of the broadly neutralizing anti-HIV-1 antibody 2G12. Proc Natl Acad Sci USA 102:13372–13377 CrossRefGoogle Scholar
  47. 47.
    Feizi T, Fazio F, Chai W, Wong C-H (2003) Carbohydrate microarrays – a new set of technologies at the frontiers of glycomics. Curr Opin Struct Biol 13:637–645 CrossRefGoogle Scholar
  48. 48.
    Huang CY et al. (2006) Carbohydrate microarray for profiling the antibodies interacting with Globo H tumor antigen. Proc Natl Acad Sci USA 103:15–20 CrossRefGoogle Scholar
  49. 49.
    Lee MR, Shin I (2005) Facile preparation of carbohydrate microarrays by site-specific, covalent immobilization of unmodified carbohydrates on hydrazide-coated glass slides. Org Lett 7:4269–4272 CrossRefGoogle Scholar
  50. 50.
    Winssinger N, Harris JL, Backes BJ, Schultz PG (2001) From split-pool libraries to spatially addressable microarrays and its application to functional proteomic profiling. Angew Chem Int Ed 40:3152–3155 CrossRefGoogle Scholar
  51. 51.
    Harris JL, Winssinger N (2005) PNA encoding (PNA=peptide nucleic acid): from solution-based libraries to organized microarrays. Chemistry 11:6792–6801 CrossRefGoogle Scholar
  52. 52.
    Winssinger N, Ficarro S, Schultz PG, Harris JL (2002) Profiling protein function with small molecule microarrays. Proc Natl Acad Sci USA 99:11139–11144 CrossRefGoogle Scholar
  53. 53.
    Debaene F, Mejias L, Harris JL, Winssinger N (2004) Synthesis of a PNA-encoded cysteine protease inhibitor library. Tetrahedron 60:8677–8690 CrossRefGoogle Scholar
  54. 54.
    Urbina HD, Debaene F, Jost B, Bole-Feysot C, Mason DE, Kuzmic P, Harris JL, Winssinger N (2006) Self-assembled small molecule microarrays for protease screening and profiling. ChemBioChem 7(11):1790–1797 CrossRefGoogle Scholar
  55. 55.
    Winssinger N et al. (2004) PNA-encoded protease substrate microarrays. Chem Biol 11:1351–1360 CrossRefGoogle Scholar
  56. 56.
    Harris J et al. (2004) Activity profile of dust mite allergen extract using substrate libraries and functional proteomic microarrays. Chem Biol 11:1361–1372 CrossRefGoogle Scholar
  57. 57.
    Sano S, Tomizaki KY, Usui K, Mihara H (2006) A PNA-DNA hybridization chip approach for the detection of beta-secretase activity. Bioorg Med Chem Lett 16:503–506 CrossRefGoogle Scholar
  58. 58.
    Diaz-Mochon JJ, Bialy L, Keinicke L, Bradley M (2005) Combinatorial libraries – from solution to 2D microarrays. Chem Comm 7:1384–1386 CrossRefGoogle Scholar
  59. 59.
    Bryan MC et al. (2002) Saccharide display on microtiter plates. Chem Biol 9:713–720 CrossRefGoogle Scholar
  60. 60.
    Fazio F, Bryan MC, Blixt O, Paulson JC, Wong CH (2002) Synthesis of sugar arrays in microtiter plate. J Am Chem Soc 124:14397–14402 CrossRefGoogle Scholar
  61. 61.
    Studer A et al. (1997) Fluorous synthesis: a fluorous-phase strategy for improving separation efficiency in organic synthesis. Science 275:823–826 CrossRefGoogle Scholar
  62. 62.
    Ko K-S, Jaipuri FA, Pohl NL (2005) Fluorous-based carbohydrate microarrays. J Am Chem Soc 127:13162–13163 CrossRefGoogle Scholar
  63. 63.
    Gosalia DN, Diamond SL (2003) Printing chemical libraries on microarrays for fluid phase nanoliter reactions. Proc Natl Acad Sci USA 100:8721–8726 CrossRefGoogle Scholar
  64. 64.
    Bailey SN, Sabatini DM, Stockwell BR (2004) Microarrays of small molecules embedded in biodegradable polymers for use in mammalian cell-based screens. Proc Natl Acad Sci USA 101:16144–16149 CrossRefGoogle Scholar
  65. 65.
    Kumaresan PR, Lam KS (2006) Screening chemical microarrays: methods and applications. In: Bartlett P, Entzeroth M (eds) Exploiting chemical diversity for drug discovery. RSC, UK, pp 291–312 Google Scholar
  66. 66.
    Kukar T et al. (2002) Protein microarrays to detect protein–protein interactions using red and green fluorescent proteins. Anal Biochem 306:50–54 CrossRefGoogle Scholar
  67. 67.
    Sielaff I et al. (2006) Protein function microarrays based on self-immobilizing and self-labeling fusion proteins. Chem Bio Chem 7:194–202 Google Scholar
  68. 68.
    Kawahashi Y et al. (2003) In vitro protein microarrays for detecting protein–protein interactions: application of a new method for fluorescence labeling of proteins. Proteomics 3:1236–1243 CrossRefGoogle Scholar
  69. 69.
    Koehler AN, Shamji AF, Schreiber SL (2003) Discovery of an inhibitor of a transcription factor using small molecule microarrays and diversity-oriented synthesis. J Am Chem Soc 125:8420–8421 CrossRefGoogle Scholar
  70. 70.
    Kato R, Kunimatsu M, Fujimoto S, Kobayashi T, Honda H (2004) Angiotensin II inhibitory peptide found in the receptor sequence using peptide array. Biochem Biophys Res Commun 315:22–29 CrossRefGoogle Scholar
  71. 71.
    Reddy MM, Kodadek T (2005) Protein fingerprinting in complex mixtures with peptoid microarrays. Proc Natl Acad Sci USA 102:12672–12677 CrossRefGoogle Scholar
  72. 72.
    Uttamchandani M et al. (2004) Microarrays of tagged combinatorial triazine libraries in the discovery of small-molecule ligands of human IgG. J Comb Chem 6:862–868 CrossRefGoogle Scholar
  73. 73.
    Tegge W, Frank R, Hofmann F, Dostmann WR (1995) Determination of cyclic nucleotide-dependent protein kinase substrate specificity by the use of peptide libraries on cellulose paper. Biochemistry 34:10569–10577 CrossRefGoogle Scholar
  74. 74.
    Dostmann WR et al. (2000) Highly specific, membrane-permeant peptide blockers of cGMP-dependent protein kinase Iα inhibit NO-induced cerebral dilation. Proc Natl Acad Sci USA 97:14772–14777 CrossRefGoogle Scholar
  75. 75.
    Mah AS et al. (2005) Substrate specificity analysis of protein kinase complex Dbf2-Mob1 by peptide library and proteome array screening. BMC Biochem 6:22 CrossRefGoogle Scholar
  76. 76.
    Panse S et al. (2004) Profiling of generic anti-phosphopeptide antibodies and kinases with peptide microarrays using radioactive and fluorescence-based assays. Mol Divers 8:291–299 CrossRefGoogle Scholar
  77. 77.
    Rychlewski L, Kschischo M, Dong L, Schutkowski M, Reimer U (2004) Target specificity analysis of the Abl kinase using peptide microarray data. J Mol Biol 336:307–311 CrossRefGoogle Scholar
  78. 78.
    Schutkowski M et al. (2004) Automated synthesis: high-content peptide microarrays for deciphering kinase specificity and biology. Angew Chem Int Ed 43:2671–2674 CrossRefGoogle Scholar
  79. 79.
    Schutkowski M, Reineke U, Reimer U (2005) Peptide arrays for kinase profiling. ChemBioChem 6:513–521 CrossRefGoogle Scholar
  80. 80.
    Lesaicherre ML, Uttamchandani M, Chen GY, Yao SQ (2002) Antibody-based fluorescence detection of kinase activity on a peptide array. Bioorg Med Chem Lett 12:2085–2088 CrossRefGoogle Scholar
  81. 81.
    Martin K et al. (2003) Quantitative analysis of protein phosphorylation status and protein kinase activity on microarrays using a novel fluorescent phosphorylation sensor dye. Proteomics 3:1244–1255 CrossRefGoogle Scholar
  82. 82.
    Su J, Bringer MR, Ismagilov RF, Mrksich M (2005) Combining microfluidic networks and peptide arrays for multi-enzyme assays. J Am Chem Soc 127:7280–7281 CrossRefGoogle Scholar
  83. 83.
    Salisbury CM, Maly DJ, Ellman JA (2002) Peptide microarrays for the determination of protease substrate specificity. J Am Chem Soc 124:14868–14870 CrossRefGoogle Scholar
  84. 84.
    Gosalia DN, Salisbury CM, Maly DJ, Ellman JA, Diamond SL (2005) Profiling serine protease substrate specificity with solution phase fluorogenic peptide microarrays. Proteomics 5:1292–1298 CrossRefGoogle Scholar
  85. 85.
    Gosalia DN, Salisbury CM, Ellman JA, Diamond SL (2005) High throughput substrate specificity profiling of serine and cysteine proteases using solution-phase fluorogenic peptide microarrays. Mol Cell Proteomics 4:626–636 CrossRefGoogle Scholar
  86. 86.
    Park S, Lee MR, Pyo SJ, Shin I (2004) Carbohydrate chips for studying high-throughput carbohydrate–protein interactions. J Am Chem Soc 126:4812–4819 CrossRefGoogle Scholar
  87. 87.
    Park S, Shin I (2002) Fabrication of carbohydrate chips for studying protein-carbohydrate interactions. Angew Chem Int Ed 41:3180–3182 CrossRefGoogle Scholar
  88. 88.
    Adams EW et al. (2004) Oligosaccharide and glycoprotein microarrays as tools in HIV glycobiology; glycan-dependent gp120/protein interactions. Chem Biol 11:875–881 CrossRefGoogle Scholar
  89. 89.
    Houseman BT, Mrksich M (2002) Carbohydrate arrays for the evaluation of protein binding and enzymatic modification. Chem Biol 9:443–454 CrossRefGoogle Scholar
  90. 90.
    Schwarz M et al. (2003) A new kind of carbohydrate array, its use for profiling antiglycan antibodies, and the discovery of a novel human cellulose-binding antibody. Glycobiology 13:749–754 CrossRefGoogle Scholar
  91. 91.
    Kohn M et al. (2003) Staudinger ligation: a new immobilization strategy for the preparation of small-molecule arrays. Angew Chem Int Ed 42:5830–5834 CrossRefGoogle Scholar
  92. 92.
    de Paz JL, Noti C, Seeberger PH (2006) Microarrays of synthetic heparin oligosaccharides. J Am Chem Soc 128:2766–2767 CrossRefGoogle Scholar
  93. 93.
    Tully SE, Rawat M, Hsieh-Wilson LC (2006) Discovery of a TNF-alpha antagonist using chondroitin sulfate microarrays. J Am Chem Soc 128:7740–7741 CrossRefGoogle Scholar
  94. 94.
    Love KR, Seeberger PH (2002) Carbohydrate arrays as tools for glycomics. Angew Chem Int Ed 41:3583–3586 CrossRefGoogle Scholar
  95. 95.
    Manimala JC, Roach TA, Li Z, Gildersleeve JC (2006) High-throughput carbohydrate microarray analysis of 24 lectins. Angew Chem Int Ed 45:3607–3610 CrossRefGoogle Scholar
  96. 96.
    Simmons G et al. (2005) Inhibitors of cathepsin L prevent severe acute respiratory syndrome coronavirus entry. Proc Natl Acad Sci USA 102:11876–11881 CrossRefGoogle Scholar
  97. 97.
    Yeo W-S, Min D-H, Hsieh RW, Greene GL, Mrksich M (2005) Label-free detection of protein–protein interactions on biochips. Angew Chem Int Ed 44:5480–5483 CrossRefGoogle Scholar
  98. 98.
    Becker CF et al. (2005) Direct readout of protein–protein interactions by mass spectrometry from protein-DNA microarrays. Angew Chem Int Ed 44:7635–7639 CrossRefGoogle Scholar
  99. 99.
    Inamori K et al. (2005) Detection and quantification of on-chip phosphorylated peptides by surface plasmon resonance imaging techniques using a phosphate capture molecule. Anal Chem 77:3979–3985 CrossRefGoogle Scholar
  100. 100.
    Kanoh N et al. (2006) SPR imaging of photo-cross-linked small-molecule arrays on gold. Anal Chem 78:2226–2230 CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2007

Authors and Affiliations

  • Nicolas Winssinger
    • 1
    Email author
  • Zbigniew Pianowski
    • 1
  • Francois Debaene
    • 1
  1. 1.Organic and Bioorganic Chemistry LaboratoryInstitut de Science et Ingénierie Supramoléculaires, Université Louis PasteurStrasbourgFrance

Personalised recommendations