Targeting DNA quadruplexes with distamycin A and its derivatives: an ITC and NMR study |
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Authors: | Pagano Bruno Virno Ada Mattia Carlo A Mayol Luciano Randazzo Antonio Giancola Concetta |
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Institution: | Dipartimento di Scienze Farmaceutiche, Università di Salerno, via Ponte Don Melillo, 84084 Fisciano (SA), Italy. |
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Abstract: | The use of small molecules that bind and stabilize G-quadruplex structures is emerging as a promising way to inhibit telomerase activity in tumor cells. In this paper, isothermal titration calorimetry (ITC) and (1)H NMR studies have been conducted to examine the binding of distamycin A and its two carbamoyl derivatives (compounds 1 and 2) to the target d(TGGGGT)](4) and dAG(3)(T(2)AG(3))(3)] quadruplexes from the Tetrahymena and human telomeres, respectively. The interactions were examined using two different buffered solutions containing either K(+) or Na(+) at a fixed ionic strength, to evaluate any influence of the ions present in solution on the binding behaviour. Experiments reveal that distamycin A and compound 1 bind the investigated quadruplexes in both solution conditions; conversely, compound 2 appears to have a poor affinity in any case. Moreover, these studies indicate that the presence of different cations in solution affects the stoichiometry and thermodynamics of the interactions. |
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Keywords: | Quadruplex Distamycin A Derivatives Isothermal titration calorimetry NMR |
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