Diversity-Oriented Fluorescence Library Approach for Novel Sensor Development

Part of the Integrated Analytical Systems book series (ANASYS)


Fluorescence-based sensors are of extreme importance and have found applications in various fields. Although the demand for useful fluorescence sensors is acute, the conventional target-oriented approach has limited the scope and speed of novel sensor discovery. To make a breakthrough in this field, we introduced a new diversity-oriented fluorescence library approach (DOFLA) using combinatorial fluorescence compound libraries with huge structural diversity. Surprisingly, specific and unique sensors for a broad range of analytes from macromolecules including DNA, RNA, and proteins to signaling small molecules such as GTP, glutathione could be discovered from the library pools, demonstrating the universal applicability of this approach.


Combinatorial Chemistry Fluorescence Sensor Pyridinium Salt Benzimidazolium Ring Sensor Discovery 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The research and discoveries summarized herein were mainly based on the continuous contributions from the previous and present Chang group members. We are very grateful to all the individuals involved with these projects, with particular appreciations to: Dr. Gustavo R. Rosania, Dr. Shao Q. Yao, Dr. Jaeki Min, Dr. Jaewook Lee, Dr. Qian Li, Dr. Young-Hoon Ahn, Mr. Jun-Seok Lee, and Ms. Yunkyung Kim.


  1. 1.
    Valeur, B. Molecular fluorescence: Principles and applications; Wiley: Weinheim, New York, 2002Google Scholar
  2. 2.
    Lakowicz, J. R. Principles of fluorescence spectroscopy; 2nd ed.; Kluwer/Plenum: New York, 1999Google Scholar
  3. 3.
    Czarnik, A. W. Fluorescent chemosensors for ion and molecule recognition; American Chemical Society: Washington, DC, 1993CrossRefGoogle Scholar
  4. 4.
    Zhang, J.; Campbell, R. E.; Ting, A. Y.; Tsien, R. Y., Creating new fluorescent probes for cell biology, Nat Rev Mol Cell Biol 2002, 3, 906–918CrossRefGoogle Scholar
  5. 5.
    Czarnik, A. W., Desperately seeking sensors, Chem Biol 1995, 2, 423–428CrossRefGoogle Scholar
  6. 6.
    Jiang, P. J.; Guo, Z. J., Fluorescent detection of zinc in biological systems: Recent development on the design of chemosensors and biosensors, Coord Chem Rev 2004, 248, 205–229CrossRefGoogle Scholar
  7. 7.
    Beer, P. D.; Gale, P. A., Anion recognition and sensing: The state of the art and future perspectives, Angew Chem Int Ed Engl 2001, 40, 486–516CrossRefGoogle Scholar
  8. 8.
    Valeur, B.; Leray, I., Design principles of fluorescent molecular sensors for cation recognition, Coord Chem Rev 2000, 205, 3–40CrossRefGoogle Scholar
  9. 9.
    deSilva, A.; Gunaratne, H.; Gunnlaugsson, T.; Huxley, A.; McCoy, C.; Rademacher, J.; Rice, T., Signaling recognition events with fluorescent sensors and switches, Chem Rev 1997, 97, 1515–1566CrossRefGoogle Scholar
  10. 10.
    Tan, D. S., Diversity-oriented synthesis: Exploring the intersections between chemistry and biology, Nat Chem Biol 2005, 1, 74–84CrossRefGoogle Scholar
  11. 11.
    Schreiber, S. L., Target-oriented and diversity-oriented organic synthesis in drug discovery, Science 2000, 287, 1964–1969CrossRefGoogle Scholar
  12. 12.
    Fergus, S.; Bender, A.; Spring, D. R., Assessment of structural diversity in combinatorial synthesis, Curr Opin Chem Biol 2005, 9, 304–309CrossRefGoogle Scholar
  13. 13.
    Dobson, C. M., Chemical space and biology, Nature 2004, 432, 824–828CrossRefGoogle Scholar
  14. 14.
    Finney, N. S., Combinatorial discovery of fluorophores and fluorescent probes, Curr Opin Chem Biol 2006, 10, 238–245CrossRefGoogle Scholar
  15. 15.
    De Miguel, Y. R., Sanders, J. K. M., Generation and screening of synthetic receptor libraries, Curr Opin ChemBiol 1998, 2, 417–421CrossRefGoogle Scholar
  16. 16.
    Srinivasan, N.; Kilburn, J. D., Combinatorial approaches to synthetic receptors, Curr Opin Chem Biol 2004, 8, 305–310Google Scholar
  17. 17.
    Mello, J.; Finney, N., Reversing the discovery paradigm: A new approach to the combinatorial discovery of fluorescent chemosensors, J Am Chem Soc 2005, 127, 10124–10125CrossRefGoogle Scholar
  18. 18.
    Schiedel, M. S.; Briehn, C. A.; Bauerle, P., Single-compound libraries of organic materials: Parallel synthesis and screening of fluorescent dyes, Angew Chem Int Ed Engl 2001, 40, 4677–4680CrossRefGoogle Scholar
  19. 19.
    Sivakumar, K.; Xie, F.; Cash, B. M.; Long, S.; Barnhill, H. N.; Wang, Q., A fluorogenic 1,3-dipolar cycloaddition reaction of 3-azidocoumarins and acetylenes, Org Lett 2004, 6, 4603–4606CrossRefGoogle Scholar
  20. 20.
    Zhu, Q.; Yoon, H. S.; Parikh, P. B.; Chang, Y. T.; Yao, S. Q., Combinatorial discovery of novel fluorescent dyes based on dapoxyl, Tetrahedron Lett 2002, 43, 5083–5086CrossRefGoogle Scholar
  21. 21.
    Li, Q.; Lee, J.; Ha, C.; Park, C.; Yang, G.; Gan, W.; Chang, Y., Solid-phase synthesis of styryl dyes and their application as amyloid sensors, Angew Chem Int Ed Engl 2004, 43, 6331–6335CrossRefGoogle Scholar
  22. 22.
    Wang, S.; Chang, Y. T., Combinatorial synthesis of benzimidazolium dyes and its diversity directed application toward GTP-selective fluorescent chemosensors, J Am Chem Soc 2006, 128, 10380–10381CrossRefGoogle Scholar
  23. 23.
    Ahn, Y. H.; Lee, J. S.; Chang, Y. T., Combinatorial rosamine library and application to in vivo glutathione probe, J Am Chem Soc 2007, 129, 4510–4511CrossRefGoogle Scholar
  24. 24.
    Min, J., Lee, J. W., Ahn, Y. H., Chang, Y. T., Combinatorial dapoxyl dye library and its application to site selective probe for human serum albumin, J Comb Chem 2007, 9, 1079–1083CrossRefGoogle Scholar
  25. 25.
    Sudlow, G.; Birkett, D. J.; Wade, D. N., Characterization of 2 specific drug binding-sites on human-serum albumin, Mol Pharmacol 1975, 11, 824–832Google Scholar
  26. 26.
    Sudlow, G.; Birkett, D. J.; Wade, D. N., Further characterization of specific drug binding-sites on human-serum albumin, Mol Pharmacol 1976, 12, 1052–1061Google Scholar
  27. 27.
    Irikura, M.; Takadate, A.; Goya, S.; Otagiri, M., 7-alkylaminocoumarin-4-acetic acids as fluorescent-probe for studies of drug-binding sites on human serum-albumin, Chem Pharm Bull 1991, 39, 724–728Google Scholar
  28. 28.
    He, X. M.; Carter, D. C., Atomic-structure and chemistry of human serum-albumin, Nature 1992, 358, 209–215CrossRefGoogle Scholar
  29. 29.
    Rosania, G. R.; Lee, J. W.; Ding, L.; Yoon, H. S.; Chang, Y. T., Combinatorial approach to organelle-targeted fluorescent library based on the styryl scaffold, J Am Chem Soc 2003, 125, 1130–1131CrossRefGoogle Scholar
  30. 30.
    Lee, J. W.; Jung, M.; Rosania, G. R.; Chang, Y. T., Development of novel cell-permeable DNA sensitive dyes using combinatorial synthesis and cell-based screening, Chem Comm 2003, 1852–1853Google Scholar
  31. 31.
    Li, Q.; Kim, Y.; Namm, J.; Kulkarni, A.; Rosania, G. R.; Ahn, Y. H.; Chang, Y. T., RNA-selective, live cell imaging probes for studying nuclear structure and function, Chem Biol 2006, 13, 615–623CrossRefGoogle Scholar
  32. 32.
    Mizukami, S.; Nagano, T.; Urano, Y.; Odani, A.; Kikuchi, K., A fluorescent anion sensor that works in neutral aqueous solution for bioanalytical application, J Am Chem Soc 2002, 124, 3920–3925CrossRefGoogle Scholar
  33. 33.
    Li, C.; Numata, M.; Takeuchi, M.; Shinkai, S., A sensitive colorimetric and fluorescent probe based on a polythiophene derivative for the detection of ATP, Angew Chem Int Ed Engl 2005, 44, 6371–6374CrossRefGoogle Scholar
  34. 34.
    Kwon, J.; Singh, N.; Kim, H.; Kim, S.; Kim, K.; Yoon, J., Fluorescent GTP-sensing in aqueous solution of physiological pH, J Am Chem Soc 2004, 126, 8892–8893CrossRefGoogle Scholar
  35. 35.
    McCleskey, S.; Griffin, M.; Schneider, S.; McDevitt, J.; Anslyn, E., Differential receptors create patterns diagnostic for TP and GTP, J Am Chem Soc 2003, 125, 1114–1115CrossRefGoogle Scholar
  36. 36.
    Burma, D. P., GTP acts as the master key in regulating diverse physiological processes, J Sci Ind Res 1988, 47, 65–80Google Scholar
  37. 37.
    Pogson, C. I., Guanine nucleotides and their significance in biochemical processes, Am J Clin Nutr 1974, 27, 380–402Google Scholar
  38. 38.
    Moini, H.; Tirosh, O.; Park, Y. C.; Cho, K. J.; Packer, L., R-alpha-lipoic acid action on cell redox status, the insulin receptor, and glucose uptake in 3T3-L1 adipocytes, Arch Biochem Biophys 2002, 397, 384–391CrossRefGoogle Scholar
  39. 39.
    Deneke, S. M.; Fanburg, B. L., Regulation of cellular glutathione, Am J Physiol 1989, 257, L163–L173Google Scholar

Copyright information

© Springer Science + Business Media, LLC 2009

Authors and Affiliations

  1. 1.Department of ChemistryNational University of SingaporeSingapore

Personalised recommendations