Spectroscopic and Biological Studies of Phenanthroline Compounds: Selective Recognition of Gene‐Promoter G‐Quadruplex DNAs Preferred over Duplex DNA

Abstract

G-Quadruplex DNA formed in the promoter regions of proto-oncogenes would block the transcription process and eventually suppress the development of tumors, so compounds that stabilize G-quadruplex DNA are potential antitumor drugs. This article describes the interactions of three phenanthroline compounds, a-c, with proto-oncogene c-kit2 and c-myc G-quadruplex DNAs by means of polymerase chain reaction (PCR) stop assay, fluorescence resonance energy transfer melting (FRET melting) assay, fluorescence indicator displacement (FID) assay, UV/VIS absorption, fluorescence, and circular dichroism (CD) spectroscopies. All three compounds displayed selectivity for the G-quadruplex over duplex, with binding constants (Ka) for the both quadruplexes varying from 0.49×10⁶ to 3.32×10⁶ M⁻¹ (4.1- to 33.2-fold specificity). Compounds a, b, and c were potential stabilizers for the c-kit2 G-quadruplex with the melting-temperature increase (ΔTm) values of 12-15°. CD Spectra indicated that a-c disrupted the structure of c-kit2 G-quadruplex, whereas no significant change was observed for c-myc G-quadruplex.

Benzothiazole Derivatives Targeting G‐Quadruplex DNA: Synthesis, DNA Interaction and Living Cell Imaging

“…The similar effect was observed for F-c-myc-T and F-c-kit2-T G4 under the same conditions, and the respective ΔT m value is 8.9 and 7.5 °C when Circular dichroism (CD) CD spectroscopy is a perfect technique in investigating the secondary structural changes of DNA. [33] Both c-myc and c-kit2 have a positive peak at 264 nm and a negative peak at 241 nm in 10 mM Tris-HCl buffer containing 100 mM K + at pH 7.0 (Figure S9), which belongs to the parallel G4 structure, [34,35] while bcl-2 has an additional shoulder peak at 295 nm (Figure 5A), which is consistent with the reported mixed-type G4 structure. [36] When different concentrations of compounds are added, CD spectra of three G4 do not change significantly (Figures 5A and S9), indicating that the binding of 1 and 2 fails to change their conformations.…”

Design, Synthesis, and Evaluation of 2,9‐Bis[(substituted‐aminomethyl)phenyl]‐1,10‐phenanthroline Derivatives as G‐Quadruplex Ligands

“…A large number of small heterocyclic molecules have been synthesized and evaluated for their ability to interact with G‐quadruplexes . Among them are the 1,10‐phenanthroline derivatives, such as PhenDC3 and its structural analogues I , tetraaminophenanthroline II , K35, and phenanthroline‐2,9‐bistriazole III (Figure ) . These compounds have been investigated for their capacity to bind and stabilize various G4 topologies and for their selectivity for G‐quadruplex versus duplex structures.…”

“…[16] Among them are the 1,10-phenanthroline derivatives, such as PhenDC3 and its structurala nalogues I,t etraaminophenanthroline II,K 35, and phenanthroline-2,9-bistriazole III (Figure 1). [17][18][19][20][21][22][23][24][25][26][27][28] These compounds have been investigated for their capacity to bind and stabilize various G4 topologies and for their selectivity for G-quadruplex versus duplexs tructures.…”

DPA‐Substituted Carbazole Derivative as a Fluorescent Ligand for G4 DNA

“…c-MYC oligomer folds into a typical parallel-type G4 structure in a buffer solution containing K + ions as suggested by its characteristic CD signature containing a positive band at 264 nm and a negative minimum at 240 nm (Figure 4b). [39] Upon titration with the ligand Car-DPA (molar ratios of ligand/c-MYC ranging from 0 : 1 to 10 : 1), the positions of the positive and negative bands seemed to be stable, while a decrease in the molar ellipticity to a lesser extent. This suggested that the G4 structure retained the parallel topology.…”

“…To gain insights into the binding event, highlighting the morphological change induced by ligand binding to the chiral G4 structure, circular dichroism (CD) titration experiment was conducted. c‐MYC oligomer folds into a typical parallel‐type G4 structure in a buffer solution containing K + ions as suggested by its characteristic CD signature containing a positive band at 264 nm and a negative minimum at 240 nm ( Figure 4 b ) [39] . Upon titration with the ligand Car‐DPA (molar ratios of ligand/ c‐MYC ranging from 0 : 1 to 10 : 1), the positions of the positive and negative bands seemed to be stable, while a decrease in the molar ellipticity to a lesser extent.…”