Selective Binding of Distamycin A Derivative to G-Quadruplex Structure [d(TGGGGT)]4
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-quadruplexe...
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| Format: | Article |
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2010-01-01
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| Series: | Journal of Nucleic Acids |
| Online Access: | http://dx.doi.org/10.4061/2010/247137 |
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| author | Bruno Pagano Iolanda Fotticchia Stefano De Tito Carlo A. Mattia Luciano Mayol Ettore Novellino Antonio Randazzo Concetta Giancola |
| author_facet | Bruno Pagano Iolanda Fotticchia Stefano De Tito Carlo A. Mattia Luciano Mayol Ettore Novellino Antonio Randazzo Concetta Giancola |
| author_sort | Bruno Pagano |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-8c8ceca9e031469293242662a96b93b5 |
| institution | Kabale University |
| issn | 2090-021X |
| language | English |
| publishDate | 2010-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Nucleic Acids |
| spelling | doaj-art-8c8ceca9e031469293242662a96b93b52025-02-03T01:32:58ZengWileyJournal of Nucleic Acids2090-021X2010-01-01201010.4061/2010/247137247137Selective Binding of Distamycin A Derivative to G-Quadruplex Structure [d(TGGGGT)]4Bruno Pagano0Iolanda Fotticchia1Stefano De Tito2Carlo A. Mattia3Luciano Mayol4Ettore Novellino5Antonio Randazzo6Concetta Giancola7Dipartimento di Scienze Farmaceutiche, Università di Salerno, Via Ponte don Melillo, 84084 Fisciano, ItalyDipartimento di Chimica “P. Corradini”, Università di Napoli Federico II, Via Cintia, 80126 Napoli, ItalyDipartimento di Chimica delle Sostanze Naturali, Università di Napoli Federico II, Via D. Montesano 49, 80131 Napoli, ItalyDipartimento di Scienze Farmaceutiche, Università di Salerno, Via Ponte don Melillo, 84084 Fisciano, ItalyDipartimento di Chimica delle Sostanze Naturali, Università di Napoli Federico II, Via D. Montesano 49, 80131 Napoli, ItalyDipartimento di Chimica Farmaceutica e Tossicologica, Università di Napoli Federico II, Via D. Montesano 49, 80131 Napoli, ItalyDipartimento di Chimica delle Sostanze Naturali, Università di Napoli Federico II, Via D. Montesano 49, 80131 Napoli, ItalyDipartimento di Chimica “P. Corradini”, Università di Napoli Federico II, Via Cintia, 80126 Napoli, ItalyGuanine-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.http://dx.doi.org/10.4061/2010/247137 |
| spellingShingle | Bruno Pagano Iolanda Fotticchia Stefano De Tito Carlo A. Mattia Luciano Mayol Ettore Novellino Antonio Randazzo Concetta Giancola Selective Binding of Distamycin A Derivative to G-Quadruplex Structure [d(TGGGGT)]4 Journal of Nucleic Acids |
| title | Selective Binding of Distamycin A Derivative to G-Quadruplex Structure [d(TGGGGT)]4 |
| title_full | Selective Binding of Distamycin A Derivative to G-Quadruplex Structure [d(TGGGGT)]4 |
| title_fullStr | Selective Binding of Distamycin A Derivative to G-Quadruplex Structure [d(TGGGGT)]4 |
| title_full_unstemmed | Selective Binding of Distamycin A Derivative to G-Quadruplex Structure [d(TGGGGT)]4 |
| title_short | Selective Binding of Distamycin A Derivative to G-Quadruplex Structure [d(TGGGGT)]4 |
| title_sort | selective binding of distamycin a derivative to g quadruplex structure d tggggt 4 |
| url | http://dx.doi.org/10.4061/2010/247137 |
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