A dual-site simultaneous binding mode in the interaction between parallel-stranded G-quadruplex [d(TGGGGT)] 4 and cyanine dye 2,2′-diethyl-9-methyl-selenacarbocyanine bromide

Abstract

G-quadruplexes have attracted growing attention as a potential cancer-associated target for both treatment and detection in recent years. For detection purpose, high specificity is one of the most important factors to be considered in G-quadruplex probe design. It is well known that end stacking and groove binding are two dominated quadruplex-ligand binding modes, and currently most reported G-quadruplex probes are designed based on the former, which has been proven to show good selectivity between quadruplexes and non-quadruplexes. Because groove of G-quadruplex also has some unique chemical properties, it could be inferred that probes that can interact with both the groove and G-tetrad site of certain G-quadruplexes simultaneously might possess higher specificity in aspects of discriminating different quadruplexes. In this article, we report a cyanine dye as a potential novel probe scaffold that could occupy both the 5′-end external G-tetrad and the corresponding groove of the G-quadruplex simultaneously. By using various spectrum and nuclear magnetic resonance techniques, we give a detailed binding characterization for this dual-site simultaneous binding mode. A preliminary result suggests that this mode might provide highly specific recognition to a parallel-stranded G-quadruplex. These findings and the structural elucidation might give some clues in aspects of developing highly specific G-quadruplex probes.

Recognizing parallel-stranded G-quadruplex by cyanine dye dimer based on dual-site binding mode

“…This result indicates that these DNA motifs do not have the proper groove conformation and cannot induce DMSB to assemble into dimers. In addition, our previous data have shown that DMSB could stabilize parallel c-myc-2345 G4 while antiparallel-stranded H22 G4 and duplex CT nearly could not, indicating that dual-site binding mode of DMSB also resulted in higher affinity to parallel G4 [19]. Further, we compare recognition ability of specific G4s by the dual-site binding mode of end-stacking.…”

“…This result strongly suggests there are two different binding modes in the interaction between TG4T and DMSB, called D-mode (stage of monomer assembling to dimer) in the case of [DMSB]/[TG4T] > 3 and M-mode (stage of dimer disassembling to monomer) in the case of [DMSB]/[TG4T] < 3. Our group has revealed that DMSB adopt a dual-site simultaneous binding mode of TG4T [19]. These results suggest that in M-mode DMSB stacks on the 3 0 -end of TG4T in the form of monomer, whereas in D-mode, DMSB could bind to the G-quadruplex in two different modes simultaneously in the form of monomer and groove-binding in dimer.…”

“…In our previous work, we reported that cyanine dye DMSB (Fig. 1), 2, 2 0 -diethyl-9-methyl-selenacarbocyanine bromide, interacted with intermolecular parallel-stranded G4 [d (TGGGGT)] 4 (abbreviated TG4T) by dual-site simultaneous binding mode, occupying the 5 0 -end terminal G-tetrad and the corresponding groove [19].…”

Photonic DNA-Chromophore Nanowire Networks: Harnessing Multiple Supramolecular Assembly Modes

“…For instance, the Armitage group has observed that the carbocyanine dye DiSC(3) binds to a folded intramolecular quadruplex with a 1:1 stoichiometry. 58 However, the nature of the cyanine dye is salient since another cyanine-based chromophore, DMSB, is also capable of binding to tetramolecular quadruplex DNA in a 2:1 fashion (where the dye forms a stacked homo-dimer) 59 . The incorporation of such cyanine based homodimers, or even chromophore tethered quadruplex DNA binding ligands (such as Distamycin A) 60 that bind to quadruplex DNA with higher stoichiometry, may allow for further enhancement of the amount of light energy funneled into the porphyrin acceptor within the nanowire scaffold.…”

Spectroscopic Investigation on the Binding of a Cyanine Dye with Transferrin

“…1), have been given particular attention in recent years. A higher sensitivity to environment and fluorescence enhancement effect of ETC for binding with biomolecules makes it be widely used in non-covalent label, [7] diagnostic probe [8] and DNA sequences applications, [16,17] and so on. The complexes of anticancer drugs and Tf are taken up by the cells through receptor-mediated endocytosis.…”