Elucidation of DNA-Eltrombopag Binding: Electrochemical, Spectroscopic and Molecular Docking Techniques

Somaye Cheraghi, Pelin Şenel, Burcu Dogan Topal, Soykan Agar, Mahsa Majidian, Mine Yurtsever, Esen Bellur Atici, Ayşegül Gölcü*, Sibel A. Ozkan*

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Özet

Eltrombopag is a powerful adjuvant anticancer drug used in treating MS (myelodysplastic syndrome) and AML (acute myeloid leukemia) diseases. In this study, the interaction mechanism between eltrombopag and DNA was studied by voltammetry, spectroscopic techniques, and viscosity measurements. We developed a DNA-based biosensor and nano-biosensor using reduced graphene oxide-modified glassy carbon electrode to detect DNA-eltrombopag binding. The reduction of desoxyguanosine (dGuo) and desoxyadenosine (dAdo) oxidation signals in the presence of the drug demonstrated that a strong interaction could be established between the eltrombopag and dsDNA. The eltrombopag-DNA interaction was further investigated by UV absorption and fluorescence emission spectroscopy to gain more quantitative insight on binding. Viscosity measurements were utilized to characterize the binding mode of the drug. To shed light on the noncovalent interactions and binding mechanism of eltrombopag molecular docking and molecular dynamics (MD), simulations were performed. Through simultaneously carried out experimental and in silico studies, it was established that the eltrombopag binds onto the DNA via intercalation.

Orijinal dilİngilizce
Makale numarası300
DergiBiosensors
Hacim13
Basın numarası3
DOI'lar
Yayın durumuYayınlandı - Mar 2023

Bibliyografik not

Publisher Copyright:
© 2023 by the authors.

Finansman

Somaye Cheraghi is grateful for the financial support of the Scientific and Technological Research Council of Turkey (TUBITAK) for this work under the BIDEB/2221 (2221/11, visiting scientists program). The authors acknowledge the financial support granted by the Istanbul Technical University (Scientific Research Projects Unit) under TDK-2020-42630 project. The authors offer their gratitude to the Scientific Research Projects Unit of Ankara University for providing financial support within Project 20B0237004. M.Y. acknowledges the computer time provided by the National High-Performance Computing Center (UHEM) under grant number 5004452017. We sincerely thank Bünyamin Karagoz (ITU, Chemistry Dep.) who allowed us to carry out the fluorescence measurements in his laboratory. We are grateful to Filiz Altay for the viscosity measurements (ITU, Department of Food Engineering, Faculty of Chemical and Metallurgical Engineering).

FinansörlerFinansör numarası
Ankara Universitesi5004452017, 20B0237004
Türkiye Bilimsel ve Teknolojik Araştırma Kurumu2221/11, BIDEB/2221
Istanbul Teknik ÜniversitesiTDK-2020-42630

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