Analytical and Bioanalytical Chemistry

, Volume 410, Issue 26, pp 6713–6717 | Cite as

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

  • Yudai Tabuchi
  • Masumi TakiEmail author


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.

Graphical abstract

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.


Fluorescent HSA binder Dynamic combinatorial library Schiff base Size-exclusion chromatography Hydrolysis Protein-ligand docking simulation 


Funding information

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.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

216_2018_1303_MOESM1_ESM.pdf (989 kb)
ESM 1 (PDF 989 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Engineering Science, Bioscience and Technology Program, The Graduate School of Informatics and EngineeringThe University of Electro-Communications (UEC)ChofuJapan

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