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Journal of Nucleic Acids
Volume 2010 (2010), Article ID 247137, 7 pages
http://dx.doi.org/10.4061/2010/247137
Research Article

Selective Binding of Distamycin A Derivative to G-Quadruplex Structure [d(TGGGGT)]4

1Dipartimento di Scienze Farmaceutiche, Università di Salerno, Via Ponte don Melillo, 84084 Fisciano, Italy
2Dipartimento di Chimica “P. Corradini”, Università di Napoli Federico II, Via Cintia, 80126 Napoli, Italy
3Dipartimento di Chimica delle Sostanze Naturali, Università di Napoli Federico II, Via D. Montesano 49, 80131 Napoli, Italy
4Dipartimento di Chimica Farmaceutica e Tossicologica, Università di Napoli Federico II, Via D. Montesano 49, 80131 Napoli, Italy

Received 21 January 2010; Accepted 7 March 2010

Academic Editor: Jean Louis Mergny

Copyright © 2010 Bruno Pagano et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Guanine-rich nucleic acid sequences can adopt G-quadruplex structures stabilized by layers of four Hoogsteen-paired guanine residues. Quadruplex-prone sequences are found in many regions of human genome and in the telomeres of all eukaryotic organisms. Since small molecules that target G-quadruplexes have been found to be effective telomerase inhibitors, the identification of new specific ligands for G-quadruplexes is emerging as a promising approach to develop new anticancer drugs. Distamycin A is known to bind to AT-rich sequences of duplex DNA, but it has recently been shown to interact also with G-quadruplexes. Here, isothermal titration calorimetry (ITC) and NMR techniques have been employed to characterize the interaction between a dicationic derivative of distamycin A (compound 1) and the [d(TGGGGT)]4 quadruplex. Additionally, to compare the binding behaviour of netropsin and compound 1 to the same target, a calometric study of the interaction between netropsin and [d(TGGGGT)]4 has been performed. Experiments show that netropsin and compound 1 are able to bind to [d(TGGGGT)]4 with good affinity and comparable thermodynamic profiles. In both cases the interactions are entropically driven processes with a small favourable enthalpic contribution. Interestingly, the structural modifications of compound 1 decrease the affinity of the ligand toward the duplex, enhancing the selectivity.