title: Targeting DNA quadruplexes with distamycin A and its derivatives: an ITC and NMR study.
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 1H 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 d[AG3(T2AG3)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.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Salerno, via Ponte Don Melillo, 84084 Fisciano (SA), Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Pagano
authors.forename: Ada
authors.initials: A
authors.lastname: Virno
authors.forename: Carlo A
authors.initials: CA
authors.lastname: Mattia
authors.forename: Luciano
authors.initials: L
authors.lastname: Mayol
authors.forename: Antonio
authors.initials: A
authors.lastname: Randazzo
authors.forename: Concetta
authors.initials: C
authors.lastname: Giancola
mesh_terms: D001483:Base Sequence; D002021:Buffers; D002151:Calorimetry; D004247:DNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D004214:Distamycins / Q000737:chemistry* / Q000378:metabolism*; D054856:G-Quadruplexes; D009682:Magnetic Resonance Spectroscopy; D011188:Potassium / Q000737:chemistry; D012964:Sodium / Q000737:chemistry; D013816:Thermodynamics; D017186:Titrimetry
chemical_list: D002021:Buffers; D004214:Distamycins; C030000:stallimycin; D004247:DNA; D012964:Sodium; D011188:Potassium