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Molecular insight into drugs binding to ctDNA: the fluorescence fast kinetic analysis of diclofenac and pentamidine

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Abstract

Diclofenac and pentamidine are renowned drugs able to bind DNA by groove-binding mechanisms. Even though the binding mechanism is known, accurate kinetic constants of the binary interaction have never been directly measured. The present work reports the study of the interaction between ctDNA and the two drugs, with very different molecular structure, by steady-state and stopped-flow fluorescence. From the stopped-flow kinetic measurements, we calculated the association and dissociation rate constants (kon and koff). The kinetic constants were then used to calculate the equilibrium dissociation binding constant (KD) and the values have been compared with what obtained from steady-state fluorescence.

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Acknowledgements

The authors acknowledge the financial support from the University of Torino (Ricerca Locale ex-60%, Bando 2019 and 2020) and from the Fondazione Cassa di Risparmio (CRT) di Torino, Italy.

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Authors and Affiliations

  1. Department of Molecular Biotechnology and Health Science, University of Torino, Via Quarello 15, 10135, Turin, Italy

    Cosmin Butnarasu & Sonja Visentin

  2. Department of Chemistry, NIS Interdepartmental Centre and INSTM Reference Centre, University of Torino, Via Pietro Giuria 7, 10125, Turin, Italy

    Nadia Barbero

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  1. Cosmin Butnarasu
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  2. Nadia Barbero
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  3. Sonja Visentin
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Correspondence to Sonja Visentin.

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Butnarasu, C., Barbero, N. & Visentin, S. Molecular insight into drugs binding to ctDNA: the fluorescence fast kinetic analysis of diclofenac and pentamidine. Monatsh Chem 153, 105–111 (2022). https://doi.org/10.1007/s00706-021-02876-7

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  • DOI: https://doi.org/10.1007/s00706-021-02876-7

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