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Interaction of G-Quadruplexes with Nonintercalating Duplex-DNA Minor Groove Binding Ligands

Jain, Akash K and Bhattacharya, Santanu (2011) Interaction of G-Quadruplexes with Nonintercalating Duplex-DNA Minor Groove Binding Ligands. In: Bioconjugate Chemistry, 22 (12). pp. 2355-2368.

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Official URL: http://pubs.acs.org/doi/abs/10.1021/bc200268a

Abstract

The enzyme telomerase synthesizes the G-rich DNA strands of the telomere and its activity is often associated with cancer. The telomerase may be therefore responsible for the ability of a cancer cell-to escape apoptosis. The G-rich DNA sequences often adopt tetra-stranded structure, known as the G-quadruplex DNA (G4-DNA). The stabilization of the telomeric DNA into the G4-DNA structures by small molecules has been the focus of many researchers for the design and development of new anticancer agents. The compounds which stabilize the G-quadruplex in the telomere inhibit the telomerase activity. Besides telomeres, the G4-DNA forming sequences are present in the genomic regions of biological significance including the transcriptional regulatory and promoter regions of several oncogenes. Inducing a G-quadruplex structure within the G-rich promoter sequences is a potential way of achieving selective gene regulation. Several G-quadruplex stabilizing ligands are known. Minor groove binding ligands (MGBLs) interact with the double-helical DNA through the minor grooves sequence-specifically and interfere with several DNA associated processes. These MGBLs when suitably modified switch their preference sometimes from the duplex DNA to G4-DNA and stabilize the G4-DNA as well. Herein, we focus on the recent advances in understanding the G-quadruplex structures, particularly made by the human telomeric ends, and review the results of various investigations of the interaction of designed organic ligands with the G-quadruplex DNA while highlighting the importance of MGBL-G-quadruplex interactions.

Item Type: Journal Article
Additional Information: Copyright of this article belongs to American Chemical Society.
Department/Centre: Division of Chemical Sciences > Organic Chemistry
Date Deposited: 27 Jan 2012 06:44
Last Modified: 27 Jan 2012 06:44
URI: http://eprints.iisc.ernet.in/id/eprint/43162

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