DNA Binding Mode Analysis of a Core-Extended Naphthalene Diimide as a Conformation-Sensitive Fluorescent Probe of G-Quadruplex Structures(289 views) Platella C, Gaglione R, Napolitano E, Arciello A, Pirota V, Doria F, Musumeci D, Montesarchio D
Department of Chemical Sciences, University of Naples Federico II, 80126 Naples, Italy.
Istituto Nazionale di Biostrutture e Biosistemi (INBB), 00136 Rome, Italy.
Institute of Biostructures and Bioimaging (IBB) of the National Research Council (CNR), 80145 Naples, Italy.
References: Not available.
DNA Binding Mode Analysis of a Core-Extended Naphthalene Diimide as a Conformation-Sensitive Fluorescent Probe of G-Quadruplex Structures
G-quadruplex existence was proved in cells by using both antibodies and small molecule fluorescent probes. However, the G-quadruplex probes designed thus far are structure- but not conformation-specific. Recently, a core-extended naphthalene diimide (c(ex)-NDI) was designed and found to provide fluorescent signals of markedly different intensities when bound to G-quadruplexes of different conformations or duplexes. Aiming at evaluating how the fluorescence behaviour of this compound is associated with specific binding modes to the different DNA targets, c(ex)-NDI was here studied in its interaction with hybrid G-quadruplex, parallel G-quadruplex, and B-DNA duplex models by biophysical techniques, molecular docking, and biological assays. c(ex)-NDI showed different binding modes associated with different amounts of stacking interactions with the three DNA targets. The preferential binding sites were the groove, outer quartet, or intercalative site of the hybrid G-quadruplex, parallel G-quadruplex, and B-DNA duplex, respectively. Interestingly, our data show that the fluorescence intensity of DNA-bound c(ex)-NDI correlates with the amount of stacking interactions formed by the ligand with each DNA target, thus providing the rationale behind the conformation-sensitive properties of c(ex)-NDI and supporting its use as a fluorescent probe of G-quadruplex structures. Notably, biological assays proved that c(ex)-NDI mainly localizes in the G-quadruplex-rich nuclei of cancer cells.
DNA Binding Mode Analysis of a Core-Extended Naphthalene Diimide as a Conformation-Sensitive Fluorescent Probe of G-Quadruplex Structures