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Fluorescent “keep-on” type pharmacophore obtained from dynamic combinatorial library of Schiff bases

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Abstract

We established a novel principle for fluorescence detection of a target protein. A low-molecular-weight fluorescent pharmacophore, as a targeted probe, was selected from a dynamic combinatorial library of Schiff bases. The pharmacophore retains its fluorescence when bound to the hydrophobic site of the target, whereas it loses it because of hydrolysis when unbound.

We describe a novel concept for detection of a target protein (i.e., HSA) by using a keep-on-type fluorescent pharmacophore which is discovered from a dynamic combinatorial library of Schiff bases. When the target is absent, the keep-on-pharmacophore is degraded by hydrolysis, with the result that we can see no fluorescence.

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References

  1. Ueno T, Nagano T. Fluorescent probes for sensing and imaging. Nat Methods. 2011;8(8):642–5.

    Article  CAS  PubMed  Google Scholar 

  2. Taki M, Inoue H, Mochizuki K, Yang J, Ito Y. Selection of color-changing and intensity-increasing fluorogenic probe as protein-specific indicator obtained via the 10BASE(d)-T. Anal Chem. 2016;88(2):1096–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Lee MH, Kim JS, Sessler JL. Small molecule-based ratiometric fluorescence probes for cations, anions, and biomolecules. Chem Soc Rev. 2015;44(13):4185–91.

    Article  CAS  PubMed  Google Scholar 

  4. Fujita H, Kataoka Y, Tobita S, Kuwahara M, Sugimoto N. Novel one-tube-one-step real-time methodology for rapid transcriptomic biomarker detection: signal amplification by ternary initiation complexes. Anal Chem. 2016;88(14):7137–44.

    Article  CAS  PubMed  Google Scholar 

  5. Chan J, Dodani SC, Chang CJ. Reaction-based small-molecule fluorescent probes for chemoselective bioimaging. Nat Chem. 2012;4(12):973–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Kawaguchi M, Okabe T, Okudaira S, Hanaoka K, Fujikawa Y, Terai T, et al. Fluorescence probe for lysophospholipase C/NPP6 activity and a potent NPP6 inhibitor. J Am Chem Soc. 2011;133(31):12021–30.

    Article  CAS  PubMed  Google Scholar 

  7. Urano Y, Sakabe M, Kosaka N, Ogawa M, Mitsunaga M, Asanuma D, et al. Rapid cancer detection by topically spraying a gamma-glutamyltranspeptidase-activated fluorescent probe. Sci Transl Med. 2011;3(110):110ra9.

    Article  CAS  Google Scholar 

  8. Vendrell M, Zhai D, Er JC, Chang YT. Combinatorial strategies in fluorescent probe development. Chem Rev. 2012;112(8):4391–420.

    Article  CAS  PubMed  Google Scholar 

  9. Ljosa V, Carpenter AE. High-throughput screens for fluorescent dye discovery. Trends Biotechnol. 2008;26(10):527–30.

    Article  CAS  PubMed  Google Scholar 

  10. Poronik YM, Bernas T, Wrzosek A, Banasiewicz M, Szewczyk A, Gryko DT. One-photon and two-photon mitochondrial fluorescent probes based on a Rhodol chromophore. Asian J Org Chem. 2018;7(2):411–5.

    Article  CAS  Google Scholar 

  11. Liu TT, Gao YQ, Zhang XM, Wan YC, Du LP, Fang H, et al. Discovery of a turn-on fluorescent probe for myeloid cell leukemia-1 protein. Anal Chem. 2017;89(21):11173–7.

    Article  CAS  PubMed  Google Scholar 

  12. Zhang YJ, Yan J, Yao TP. Discovery of a fluorescent probe with HDAC6 selective inhibition. Eur J Med Chem. 2017;141:596–602.

    Article  CAS  PubMed  Google Scholar 

  13. Kelly PM, Keely NO, Bright SA, Yassin B, Ana G, Fayne D, et al. Novel selective estrogen receptor ligand conjugates incorporating endoxifen-combretastatin and cyclofenil-combretastatin hybrid scaffolds: synthesis and biochemical evaluation. Molecules. 2017;22(9):1440.

    Article  CAS  Google Scholar 

  14. Huang XY, Aulabaugh A. Application of fluorescence polarization in HTS assays. High throughput screening: methods and protocols, 3rd Edition. 2016;1439:115–30.

  15. Hall MD, Yasgar A, Peryea T, Braisted JC, Jadhav A, Simeonov A, et al. Fluorescence polarization assays in high-throughput screening and drug discovery: a review. Methods Appl Fluoresc. 2016;4(2):022001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Levitt JA, Matthews DR, Ameer-Beg SM, Suhling K. Fluorescence lifetime and polarization-resolved imaging in cell biology. Curr Opin Biotechnol. 2009;20(1):28–36.

    Article  CAS  PubMed  Google Scholar 

  17. Lea WA, Simeonov A. Fluorescence polarization assays in small molecule screening. Expert Opin Drug Discovery. 2011;6(1):17–32.

    Article  CAS  Google Scholar 

  18. Burchak ON, Mugherli L, Ostuni M, Lacapere JJ, Balakirev MY. Combinatorial discovery of fluorescent pharmacophores by multicomponent reactions in droplet arrays. J Am Chem Soc. 2011;133(26):10058–61.

    Article  CAS  PubMed  Google Scholar 

  19. Yun SW, Kang NY, Park SJ, Ha HH, Kim YK, Lee JS, et al. Diversity oriented fluorescence library approach (DOFLA) for live cell imaging probe development. Acc Chem Res. 2014;47(4):1277–86.

    Article  CAS  PubMed  Google Scholar 

  20. Ramstrom O, Lehn JM. Drug discovery by dynamic combinatorial libraries. Nat Rev Drug Discov. 2002;1(1):26–36.

    Article  CAS  PubMed  Google Scholar 

  21. Mondal M, Hirsch AK. Dynamic combinatorial chemistry: a tool to facilitate the identification of inhibitors for protein targets. Chem Soc Rev. 2015;44(8):2455–88.

    Article  CAS  PubMed  Google Scholar 

  22. Li J, Nowak P, Otto S. Dynamic combinatorial libraries: from exploring molecular recognition to systems chemistry. J Am Chem Soc. 2013;135(25):9222–39.

    Article  CAS  PubMed  Google Scholar 

  23. Herrmann A. Dynamic combinatorial/covalent chemistry: a tool to read, generate and modulate the bioactivity of compounds and compound mixtures. Chem Soc Rev. 2014;43(6):1899–933.

    Article  CAS  PubMed  Google Scholar 

  24. Huang R, Leung IK. Protein-directed dynamic combinatorial chemistry: a guide to protein ligand and inhibitor discovery. Molecules. 2016;21(7):910.

    Article  CAS  Google Scholar 

  25. Huc I, Lehn JM. Virtual combinatorial libraries: dynamic generation of molecular and supramolecular diversity by self-assembly. Proc Natl Acad Sci U S A. 1997;94(6):2106–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Zhang X, Yin J, Yoon J. Recent advances in development of chiral fluorescent and colorimetric sensors. Chem Rev. 2014;114(9):4918–59.

    Article  CAS  PubMed  Google Scholar 

  27. Fang Z, He W, Li X, Li Z, Chen B, Ouyang P, et al. A novel protocol to accelerate dynamic combinatorial chemistry via isolation of ligand-target adducts from dynamic combinatorial libraries: a case study identifying competitive inhibitors of lysozyme. Bioorg Med Chem Lett. 2013;23(18):5174–7.

    Article  CAS  PubMed  Google Scholar 

  28. Yang Z, Fang Z, He W, Wang Z, Gan H, Tian Q, et al. Identification of inhibitors for vascular endothelial growth factor receptor by using dynamic combinatorial chemistry. Bioorg Med Chem Lett. 2016;26(7):1671–4.

    Article  CAS  PubMed  Google Scholar 

  29. Er JC, Vendrell M, Tang MK, Zhai D, Chang YT. Fluorescent dye cocktail for multiplex drug-site mapping on human serum albumin. ACS Comb Sci. 2013;15(9):452–7.

    Article  CAS  PubMed  Google Scholar 

  30. Shen P, Hua JY, Jin HD, Du JY, Liu CL, Yang W, et al. Recognition and quantification of HSA: a fluorescence probe across alpha-helices of site I and site II. Sensors Actuators B Chem. 2017;247:587–94.

    Article  CAS  Google Scholar 

  31. Oettl K, Stauber RE. Physiological and pathological changes in the redox state of human serum albumin critically influence its binding properties. Brit J Pharmacol. 2007;151(5):580–90.

    Article  CAS  Google Scholar 

  32. Fukunishi Y, Mikami Y, Nakamura H. Similarities among receptor pockets and among compounds: analysis and application to in silico ligand screening. J Mol Graph Model. 2005;24(1):34–45.

    Article  CAS  PubMed  Google Scholar 

  33. Fukunishi Y, Mikami Y, Nakamura H. The filling potential method: a method for estimating the free energy surface for protein-ligand docking. J Phys Chem B. 2003;107(47):13201–10.

    Article  CAS  Google Scholar 

  34. Sasaki S, Drummen GPC, Konishi G. Recent advances in twisted intramolecular charge transfer (TICT) fluorescence and related phenomena in materials chemistry. J Mater Chem C. 2016;4(14):2731–43.

    Article  CAS  Google Scholar 

  35. Janzen WP. Screening technologies for small molecule discovery: the state of the art. Chem Biol. 2014;21(9):1162–70.

    Article  CAS  PubMed  Google Scholar 

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Funding

This work was supported by a JSPS KAKENHI grant (#17K05925) to M.T. We are grateful to Prof. Dr. K. Ikebukuro and Dr. J. Lee (TUAT) for use of the ITC instrument installed by the grant from the Low-Carbon Research Network Japan (LCnet). We appreciate Dr. L. Nelson (MD Anderson), Prof. T. Yamashita (Keio Univ.), and Prof. M. Tanaka (UEC) for critical reading of this manuscript. We also thank to Dr. H. Nakamura (Biomodeling Research Inc.) for fruitful discussions about molecular modeling.

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Authors and Affiliations

  1. Department of Engineering Science, Bioscience and Technology Program, The Graduate School of Informatics and Engineering, The University of Electro-Communications (UEC), 1-5-1 Chofugaoka, Chofu, Tokyo, 182-8585, Japan

    Yudai Tabuchi & Masumi Taki

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  1. Yudai Tabuchi
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  2. Masumi Taki
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Correspondence to Masumi Taki.

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Tabuchi, Y., Taki, M. Fluorescent “keep-on” type pharmacophore obtained from dynamic combinatorial library of Schiff bases. Anal Bioanal Chem 410, 6713–6717 (2018). https://doi.org/10.1007/s00216-018-1303-4

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