title: Selective Binding of Distamycin A Derivative to G-Quadruplex Structure [d(TGGGGT)](4).
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.
authors: Dipartimento di Scienze Farmaceutiche, Università di Salerno, Via Ponte don Melillo, 84084 Fisciano, Italy.
authors: Bruno
authors: B
authors: Pagano
authors: Iolanda
authors: I
authors: Fotticchia
authors: Stefano
authors: S
authors: De Tito
authors: Carlo A
authors: CA
authors: Mattia
authors: Luciano
authors: L
authors: Mayol
authors: Ettore
authors: E
authors: Novellino
authors: Antonio
authors: A
authors: Randazzo
authors: Concetta
authors: C
authors: Giancola