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A DNA Biosensor Based on a Raspberry-like Hierarchical Nano-structure for the Determination of the Anticancer Drug Nilotinib.

ABSTRACT: It is crucial to design fast, sensitive and affordable deoxyribonucleic acid (DNA) recognition instruments, and elucidate changes in DNA structure, for studying the interaction between DNA and chemotherapy drugs. Therefore, a DNA biosensor, based on a carbon paste electrode (CPE), modified with raspberry-like indium(III)/nickel oxide hierarchical nano-structures (In³⁺ /NiO RLHNSs) was constructed. An electrochemical readout should then give information on the interactions between anticancer drugs and double-stranded (ds)-DNA. The morphology as well as the electrochemical description of this new biosensor is described. Based on experimentally determined optimal conditions, ds-DNA modified with In³⁺ /NiO RLHNSs/CPE was used to evaluate the binding interaction of nilotinib, as an anti-cancer drug, with DNA through differential pulse voltammetry (DPV), UV-Vis spectroscopy, viscosity measurements and a computational docking process. The analyses indicated the linearity of the guanine oxidation signal at nilotinib concentration is given between 0.01 and 50.0 μm, with the limit of detection (LOD) equal to 0.62 nm. Additionally, the equilibrium constant (K) for the binding was determined to 1.5×10⁴ m^-1 . Through the quantitative measurement of nilotinib in serum samples with a high recovery rate of 101.3-98.0 %, the applicability of this approach was demonstrated. As a whole, this DNA biosensor may be promising for various bio-interactions.

SUBMITTER: Moarefdoust MM

PROVIDER: S-EPMC8950773 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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A DNA Biosensor Based on a Raspberry-like Hierarchical Nano-structure for the Determination of the Anticancer Drug Nilotinib.

Moarefdoust Mohammad Mehdi MM Jahani Shohreh S Moradalizadeh Mehran M Motaghi Mohammad Mehdi MM Foroughi Mohammad Mehdi MM

ChemistryOpen 20220301 3

It is crucial to design fast, sensitive and affordable deoxyribonucleic acid (DNA) recognition instruments, and elucidate changes in DNA structure, for studying the interaction between DNA and chemotherapy drugs. Therefore, a DNA biosensor, based on a carbon paste electrode (CPE), modified with raspberry-like indium(III)/nickel oxide hierarchical nano-structures (In<sup>3+</sup> /NiO RLHNSs) was constructed. An electrochemical readout should then give information on the interactions between anti ...[more]

PMID: 35333006

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Project description:Single-stranded DNA-binding proteins (SSBs) play a crucial role in DNA metabolism by binding and stabilizing single-stranded DNA (ssDNA) intermediates. Through their multifaceted roles in DNA replication, recombination, repair, replication restart, and other cellular processes, SSB emerges as a central player in maintaining genomic integrity. These attributes collectively position SSBs as essential guardians of genomic integrity, establishing interactions with an array of distinct proteins. Unlike Escherichia coli, which contains only one type of SSB, some bacteria have two paralogous SSBs, referred to as SsbA and SsbB. In this study, we identified Staphylococcus aureus SsbA (SaSsbA) as a fresh addition to the roster of the anticancer drug 5-fluorouracil (5-FU) binding proteins, thereby expanding the ambit of the 5-FU interactome to encompass this DNA replication protein. To investigate the binding mode, we solved the complexed crystal structure with 5-FU at 2.3 Å (PDB ID 7YM1). The structure of glycerol-bound SaSsbA was also determined at 1.8 Å (PDB ID 8GW5). The interaction between 5-FU and SaSsbA was found to involve R18, P21, V52, F54, Q78, R80, E94, and V96. Based on the collective results from mutational and structural analyses, it became evident that SaSsbA's mode of binding with 5-FU diverges from that of SaSsbB. This complexed structure also holds the potential to furnish valuable comprehension regarding how 5-FU might bind to and impede analogous proteins in humans, particularly within cancer-related signaling pathways. Leveraging the information furnished by the glycerol and 5-FU binding sites, the complexed structures of SaSsbA bring to the forefront the potential viability of several interactive residues as potential targets for therapeutic interventions aimed at curtailing SaSsbA activity. Acknowledging the capacity of microbiota to influence the host's response to 5-FU, there emerges a pressing need for further research to revisit the roles that bacterial and human SSBs play in the realm of anticancer therapy.

Dataset Information

A DNA Biosensor Based on a Raspberry-like Hierarchical Nano-structure for the Determination of the Anticancer Drug Nilotinib.

Publications

A DNA Biosensor Based on a Raspberry-like Hierarchical Nano-structure for the Determination of the Anticancer Drug Nilotinib.

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