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Dimeric 1,3-Phenylene-bis(piperazinyl benzimidazole)s: Synthesis and Structure-Activity Investigations on their Binding with Human Telomeric G-Quadruplex DNA and Telomerase Inhibition Properties

Jain, Akash K and Paul, Ananya and Maji, Basudeb and Muniyappa, K and Bhattacharya, Santanu (2012) Dimeric 1,3-Phenylene-bis(piperazinyl benzimidazole)s: Synthesis and Structure-Activity Investigations on their Binding with Human Telomeric G-Quadruplex DNA and Telomerase Inhibition Properties. In: Journal of Medicinal Chemistry, 55 (7). pp. 2981-2993.

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Official URL: http://pubs.acs.org/doi/abs/10.1021/jm200860b

Abstract

Ligand-induced stabilization of G-quadruplex structures formed by the human telomeric DNA is an active area of research. The compounds which stabilize the G-quadruplexes often lead to telomerase inhibition. Herein we present the results of interaction of new monomeric and dimeric ligands having 1,3-phenylene-bis(piperazinyl benzimidazole) unit with G-quadruplex DNA (G4DNA) formed by human telomeric repeat d(G(3)T(2)A)(3)G(3)]. These ligands efficiently stabilize the preformed G4DNA in the presence of 100 mM monovalent alkali metal ions. Also, the G4DNA formed in the presence of low concentrations of ligands in 100 mM K+ adopts a highly stable parallel-stranded conformation. The G-quadruplexes formed in the presence of the dimeric compound are more stable than that induced by the corresponding monomeric counterpart. The dimeric ligands having oligo-oxyethylene spacers provide much higher stability to the preformed G4DNA and also exert significantly higher telomerase inhibition activity. Computational aspects have also been discussed.

Item Type: Journal Article
Additional Information: Copyright of this article is belongs to American Chemical Society.
Department/Centre: Division of Biological Sciences > Biochemistry
Division of Chemical Sciences > Organic Chemistry
Date Deposited: 22 Aug 2012 05:00
Last Modified: 22 Aug 2012 05:00
URI: http://eprints.iisc.ernet.in/id/eprint/44463

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