| Autor: |
Bruno Pagano, Iolanda Fotticchia, Stefano De Tito, Carlo A. Mattia, Luciano Mayol, Ettore Novellino, Antonio Randazzo, Concetta Giancola |
| Jazyk: |
angličtina |
| Rok vydání: |
2010 |
| Předmět: |
|
| Zdroj: |
Journal of Nucleic Acids, Vol 2010 (2010) |
| Druh dokumentu: |
article |
| ISSN: |
2090-021X |
| DOI: |
10.4061/2010/247137 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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