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Issue 11, 2018
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Controlling anticancer drug mediated G-quadruplex formation and stabilization by a molecular container

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Abstract

Controlling of ligand mediated G-quadruplex DNA (GQ-DNA) formation and stabilization is an important and challenging aspect due to its active involvement in many biologically important processes such as DNA replication, transcription, etc. Here, we have demonstrated that topotecan (TPT), a potential anticancer drug, can instigate the formation and stabilization of GQ-DNA (H24 → GQ-DNA) in the absence of Na+/K+ ions via circular dichroism, fluorescence, NMR, UV melting and molecular dynamics (MD) simulation studies. The primary binding mode of TPT to GQ was found to be stacking at the terminal rather than binding to the groove. We have also reverted this conformational transition (GQ-DNA → H24) using a molecular container, cucurbit[7]uril (CB7), by means of the translocation of the drug (TPT) from GQ-DNA to its nanocavity. Importantly, we have carried out the detection of these conformational transitions using the fluorescence color switch of the drug, which is more direct and simple than some of the other methods that involve sophisticated and complex detection techniques.

Graphical abstract: Controlling anticancer drug mediated G-quadruplex formation and stabilization by a molecular container

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Publication details

The article was received on 16 Jan 2018, accepted on 13 Feb 2018 and first published on 16 Feb 2018


Article type: Paper
DOI: 10.1039/C8CP00325D
Citation: Phys. Chem. Chem. Phys., 2018,20, 7808-7818
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    Controlling anticancer drug mediated G-quadruplex formation and stabilization by a molecular container

    S. Satpathi, R. K. Singh, A. Mukherjee and P. Hazra, Phys. Chem. Chem. Phys., 2018, 20, 7808
    DOI: 10.1039/C8CP00325D

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