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Characterization of paraben substituted cyclotriphosphazenes, and a DNA interaction study with a real-time electrochemical profiling based biosensor

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Abstract

This paper describes an amperometric method for studying DNA-drug candidate interactions. It uses an automatted electrochemical biosensor (MiSens®) based on real-time electrochemical profiling and gold nanoparticles. A biochip was prepared from a 10 x 20 mm silicon dioxide wafer. The biochip surface is modified with a self-assembled monolayer and integrated into the microfluidic system. All the steps of the DNA-drug interaction assay have been performed during fluid flow. Biotinylated surface DNA has been captured on a NeutrAvidin -modified biochip surface. Hybridization of the complementary target sequence and biotinylated detection probe to the surface DNA strand was studied with and without the addition of newly synthesised drug candidates. NeutrAvidin and enzyme modified gold nanoparticles were then injected to bind to the biochip surface. The real-time reading of the amperometric response during the substrate injection results in the biosensor signal. The DNA interaction analysis was exemplarily applied to test the activity of paraben-substituted cyclotriphosphazenes as potential anticancer agents. Two of the synthesised compounds were identified that are capable of inducing DNA damage by 27 and 34%, respectively.

DNA-drug interactions can be investigated by an automated biosensor device that relies on Real-time Electrochemical Profiling (REP™).

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Acknowledgements

The authors thank to Gebze Technical University (GTU) for the provided financial support (Grant No: BAP-2013-A-013). The project is also supported by BILGEM-TUBITAK (The Scientific and Technological Research Council of Turkey; Grant no:100121). We gratefully acknowledge Bioelectronic Devices and Systems Group from BILGEM-TUBITAK for their contribution to the fabrication of the biochip and the sensing platform.

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Authors and Affiliations

  1. Department of Chemistry, Gebze Technical University, 41400 Gebze-, Kocaeli, Turkey

    Gönül Yenilmez Çiftçi, Elif Şenkuytu, Saadet Elif İncir, Esra Tanrıverdi Eçik, Yunus Zorlu & Zehra Ölçer

  2. Bioelectronic Devices and Systems Group, UEKAE - BILGEM - The Scientific and Technological Research Council of Turkey (TUBITAK), Kocaeli, 41470, Gebze, Turkey

    Yildiz Uludağ

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  1. Gönül Yenilmez Çiftçi
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  2. Elif Şenkuytu
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Correspondence to Gönül Yenilmez Çiftçi or Yildiz Uludağ.

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Electronic supplementary material

CCDC 1054940–1054943 contain the supplementary crystallographic data for this paper. These data can be obtained free of charge at www.ccdc.cam.ac.uk/conts/retrieving.html, or from the Cambridge Crystallographic Data Centre (CCDC), 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44(0)1223–336,033; email: deposit@ccdc.cam.ac.uk.

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Çiftçi, G.Y., Şenkuytu, E., İncir, S.E. et al. Characterization of paraben substituted cyclotriphosphazenes, and a DNA interaction study with a real-time electrochemical profiling based biosensor. Microchim Acta 184, 2307–2315 (2017). https://doi.org/10.1007/s00604-017-2162-y

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