Targeting human telomeric G-quadruplex DNA with curcumin and its synthesized analogues under molecular crowding conditions

Jha, Niki S and Mishra, Satyendra and Mamidi, Ashalatha S and Mishra, Archita and Jha, Shailendra K and Surolia, Avadhesha (2016) Targeting human telomeric G-quadruplex DNA with curcumin and its synthesized analogues under molecular crowding conditions. In: RSC ADVANCES, 6 (9). pp. 7474-7487.

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Abstract

The formation of telomeric G-quadruplexes has been shown to inhibit telomerase activity. Indeed, a number of small molecules capable of p-stacking with G-tetrads have shown the ability to inhibit telomerase activity through the stabilization of G-quadruplexes. Curcumin displays a wide spectrum of medicinal properties ranging from anti-bacterial, anti-viral, anti-protozoal, anti-fungal and anti-inflammatory to anti-cancer activity. We have investigated the interactions of curcumin and its structural analogues with the human telomeric sequence AG(3)(T(2)AG(3))(3) under molecular crowding conditions. Experimental studies indicated the existence of a AG(3)(T(2)AG(3))(3)/curcumin complex with binding affinity of 0.72 x 10(6) M-1 under molecular crowding conditions. The results from UV-visible absorption spectroscopy, a fluorescent TO displacement assay, circular dichroism and molecular docking studies, imply that curcumin and their analogues interact with G-quadruplex DNA via groove binding. While other analogs of curcumin studied here bind to G-quadruplexes in a qualitatively similar manner their affinities are relatively lower in comparison to curcumin. The Knoevenagel condensate, a methoxy-benzylidene derivative of curcumin, also exhibited significant binding to G-quadruplex DNA, although with two times decreased affinity. Our study establishes the potential of curcumin as a promising natural product for G-quadruplex specific ligands.

Item Type:	Journal Article
Publication:	RSC ADVANCES
Publisher:	ROYAL SOC CHEMISTRY
Additional Information:	Copy right for this article belongs to the ROYAL SOC CHEMISTRY, THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	02 Apr 2016 10:26
Last Modified:	02 Apr 2016 10:26
URI:	http://eprints.iisc.ac.in/id/eprint/53509

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