Bioimaging Probes Development by DOFLA (Diversity Oriented Fluorescence Library Approach) for in Vitro, in Vivo and Clinical Applications

Conference paper
Part of the Advances in Intelligent and Soft Computing book series (AINSC, volume 120)

Abstract

Due to the remarkable development of bioimaging probes and equipment during the last decades, we are able to see a variety of biological systems with a resolution ranging from centimeters to subnanometers. Bioimaging is now an indispensable tool for basic research and clinical diagnosis. Particularly, the application of fluorescence in optical imaging has enabled us to investigate molecular events as well as the structures in living cells and tissues. Among the fluorescent molecules, low molecular weight chemicals have great potentials to be developed as highly specific and versatile bioimaging probes. Target-specific fluorescent probes have been developed conventionally by a hypothesis-driven approach in which fluorophores are conjugated to already developed molecules such as antibody, peptide or small molecule drug. However, the fluorescence-labeled macromolecules may not be used for the detection of intracellular molecules in living cells and tagging small molecule without affecting its property is relatively challenging. To overcome these problems, we have developed Diversity Oriented Fluorescence Library (DOFL) by exploring the diverse chemical space directly around fluorophores using combinatorial chemistry. By screening DOFL in various platforms such as in vitro, cell, tissue and whole organism, we have successfully developed bioimaging probes which interact specifically with the targets. In this article, we discuss how bioimaging contributes to the development of biomedical science, why the development of new bioimaging probes is necessary and what can be achieved by DOFL approach (DOFLA).

Keywords

Positron Emission Tomography Single Photon Emission Compute Tomography Imaging Probe Deep Tissue Imaging Optical Imaging Probe 
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.

References

  1. 1.
    Ahn, Y.H., Lee, J.S., Chang, Y.T.: Combinatorial rosamine library and application to in vivo glutathione probe. J. Am. Chem. Soc. 129, 4510–4511 (2007)CrossRefGoogle Scholar
  2. 2.
    Ahn, Y.H., Lee, J.S., Chang, Y.T.: Selective human serum albumin sensor from the screening of a fluorescent rosamine library. J. Comb. Chem. 10, 376–380 (2008)CrossRefGoogle Scholar
  3. 3.
    Buller, F., Steiner, M., Frey, K., Mircsof, D., Scheuermann, J., Kalisch, M., Buhlmann, P., Supuran, C.T., Neri, D.: Selection of Carbonic Anhydrase IX Inhibitors from One Million DNA-Encoded Compounds. ACS Chem. Biol (2010)Google Scholar
  4. 4.
    Feng, S., Kim, Y.K., Yang, S., Chang, Y.T.: Discovery of a green DNA probe for live-cell imaging. Chem. Commun. (Camb) 46, 436–438 (2010)CrossRefGoogle Scholar
  5. 5.
    Hillier, L.W., Miller, R.D., Baird, S.E., Chinwalla, A., Fulton, L.A., Koboldt, D.C., Waterston, R.H.: Comparison of C. elegans and C. briggsae genome sequences reveals extensive conservation of chromosome organization and synteny. PLoS Biol. 5, e167 (2007)CrossRefGoogle Scholar
  6. 6.
    Hopkins, A.L., Groom, C.R.: The druggable genome. Nat. Rev. Drug Discov. 1, 727–730 (2002)CrossRefGoogle Scholar
  7. 7.
    Im, C.N., Kang, N.Y., Ha, H.H., Bi, X., Lee, J.J., Park, S.J., Lee, S.Y., Vendrell, M., Kim, Y.K., Lee, J.S., Li, J., Ahn, Y.H., Feng, B., Ng, H.H., Yun, S.W., Chang, Y.T.: A fluorescent rosamine compound selectively stains pluripotent stem cells. Angew Chem. Int. Ed. Engl. 49, 7497–7500 (2010)CrossRefGoogle Scholar
  8. 8.
    Keating, S.M., Clark, K.R., Stefanich, L.D., Arellano, F., Edwards, C.P., Bodary, S.C., Spencer, S.A., Gadek, T.R., Marsters Jr., J.C., Beresini, M.H.: Competition between intercellular adhesion molecule-1 and a small-molecule antagonist for a common binding site on the alphal subunit of lymphocyte function-associated antigen-1. Protein Sci. 15, 290–303 (2006)CrossRefGoogle Scholar
  9. 9.
    Lee, J.S., Kang, N.Y., Kim, Y.K., Samanta, A., Feng, S., Kim, H.K., Vendrell, M., Park, J.H., Chang, Y.T.: Synthesis of a BODIPY library and its application to the development of live cell glucagon imaging probe. J. Am. Chem. Soc. 131, 10077–10082 (2009)CrossRefGoogle Scholar
  10. 10.
    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. Commun. (Camb), 1852–1853 (2003)Google Scholar
  11. 11.
    Lee, S., Park, K., Kim, K., Choi, K., Kwon, I.C.: Activatable imaging probes with amplified fluorescent signals. Chem. Commun. (Camb), 4250–4260 (2008)Google Scholar
  12. 12.
    Li, J., Ha, H.H., Guo, L., Coomber, D., Chang, Y.T.: Discovery of novel zebrafish neural tracers by organism-based screening of a rosamine library. Chem. Commun (Camb) 46, 2932–2934 (2010)CrossRefGoogle Scholar
  13. 13.
    Li, Q., Lee, J.S., Ha, C., Park, C.B., Yang, G., Gan, W.B., Chang, Y.T.: Solid-phase synthesis of styryl dyes and their application as amyloid sensors. Angew Chem. Int. Ed. Engl. 43, 6331–6335 (2004)CrossRefGoogle Scholar
  14. 14.
    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. 13, 615–623 (2006)CrossRefGoogle Scholar
  15. 15.
    Li, Q., Min, J., Ahn, Y.H., Namm, J., Kim, E.M., Lui, R., Kim, H.Y., Ji, Y., Wu, H., Wisniewski, T., Chang, Y.T.: Styryl-based compounds as potential in vivo imaging agents for beta-amyloid plaques. Chem. Biochem. 8, 1679–1687 (2007)Google Scholar
  16. 16.
    Lieschke, G.J., Currie, P.D.: Animal models of human disease: zebrafish swim into view. Nat. Rev. Genet. 8, 353–367 (2007)CrossRefGoogle Scholar
  17. 17.
    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. 9, 1079–1083 (2007)CrossRefGoogle Scholar
  18. 18.
    Oksvold, M.P., Skarpen, E., Widerberg, J., Huitfeldt, H.S.: Fluorescent histochemical techniques for analysis of intracellular signaling. J. Histochem. Cytochem. 50, 289–303 (2002)CrossRefGoogle Scholar
  19. 19.
    Storms, R.W., Trujillo, A.P., Springer, J.B., Shah, L., Colvin, O.M., Ludeman, S.M., Smith, C.: Isolation of primitive human hematopoietic progenitors on the basis of aldehyde dehydrogenase activity. Proc. Natl. Acad. Sci. USA 96, 9118–9123 (1999)CrossRefGoogle Scholar
  20. 20.
    Wagner, B.K., Carrinski, H.A., Ahn, Y.H., Kim, Y.K., Gilbert, T.J., Fomina, D.A., Schreiber, S.L., Chang, Y.T., Clemons, P.A.: Small-molecule fluorophores to detect cell-state switching in the context of high-throughput screening. J. Am. Chem. Soc. 130, 4208–4209 (2008)CrossRefGoogle Scholar
  21. 21.
    Wang, S., Chang, Y.T.: Combinatorial synthesis of benzimidazolium dyes and its diversity directed application toward GTP-selective fluorescent chemosensors. J. Am. Chem. Soc. 128, 10380–10381 (2006)CrossRefGoogle Scholar
  22. 22.
    Wang, S., Chang, Y.T.: Discovery of heparin chemosensors through diversity oriented fluorescence library approach. Chem. Commun. (Camb), 1173–1175 (2008)Google Scholar
  23. 23.
    Wang, S., Kim, Y.K., Chang, Y.T.: Diversity-oriented fluorescence library approach (DOFLA) to the discovery of chymotrypsin sensor. J. Comb. Chem. 10, 460–465 (2008)CrossRefGoogle Scholar

Copyright information

© Springer Berlin Heidelberg 2012

Authors and Affiliations

  1. 1.Laboratory of Bioimaging Probe DevelopmentSingapore Bioimaging Consortium, Agency for Science, Technology and ResearchSingaporeRepublic of Singapore
  2. 2.Department of Chemistry & NUS MedChem Program of Life Sciences InstituteNational University of SingaporeSingaporeRepublic of Singapore

Personalised recommendations