PhenDV, a turn-off fluorescent quadruplex DNA probe for improving the sensitivity of drug screening assays.

We report a new turn-off fluorescent probe, PhenDV, for the identification of high affinity quadruplex (G4) DNA ligands. This push-pull fluorophore displays a high fluorescence quantum yield in water (Φ = 0.21) and is a selective and strong quadruplex DNA binder.

Copper-Alkyne Complexation Responsible for the Nucleolar Localization of Quadruplex Nucleic Acid Drugs Labeled by Click Reactions.

G-Quadruplex(es) (G4) are noncanonical nucleic-acid structures found in guanine-rich sequences. They can be targeted with small molecules (G4 ligands) acting as reporters, for tracking both in vitro and in cells. We explored the cellular localization of PhenDC , one of the most powerful G4 ligands, by synthesizing two clickable azide and alkyne derivatives (PhenDC -alk, PhenDC -az) and labeling them in situ with the corresponding Cy5 click partners.

Nucleolin directly mediates Epstein-Barr virus immune evasion through binding to G-quadruplexes of EBNA1 mRNA.

The oncogenic Epstein-Barr virus (EBV) evades the immune system but has an Achilles heel: its genome maintenance protein EBNA1, which is essential for viral genome maintenance but highly antigenic. EBV has seemingly evolved a system in which the mRNA sequence encoding the glycine-alanine repeats (GAr) of the EBNA1 protein limits its expression to the minimal level necessary for function while minimizing immune recognition. Here, we identify nucleolin (NCL) as a host factor required for this process via a direct interaction with G-quadruplexes formed in GAr-encoding mRNA sequence.

What stoichiometries determined by mass spectrometry reveal about the ligand binding mode to G-quadruplex nucleic acids.

G-quadruplexes (G4s) have become important drug targets to regulate gene expression and telomere maintenance. Many studies on G4 ligand binding focus on determining the ligand binding affinities and selectivities. Ligands, however, can also affect the G4 conformation.

Highly efficient radiosensitization of human glioblastoma and lung cancer cells by a G-quadruplex DNA binding compound.

Telomeres are nucleoprotein structures at the end of chromosomes which stabilize and protect them from nucleotidic degradation and end-to-end fusions. The G-rich telomeric single-stranded DNA overhang can adopt a four-stranded G-quadruplex DNA structure (G4). Stabilization of the G4 structure by binding of small molecule ligands enhances radiosensitivity of tumor cells, and this combined treatment represents a novel anticancer approach.

Impact of G-quadruplex structures and intronic polymorphisms rs17878362 and rs1642785 on basal and ionizing radiation-induced expression of alternative p53 transcripts.

G-quadruplex (G4) structures in intron 3 of the p53 pre-mRNA modulate intron 2 splicing, altering the balance between the fully spliced p53 transcript (FSp53, encoding full-length p53) and an incompletely spliced transcript retaining intron 2 (p53I2 encoding the N-terminally truncated Δ40p53 isoform). The nucleotides forming G4s overlap the polymorphism rs17878362 (A1 wild-type allele, A2 16-base pair insertion) which is in linkage disequilibrium with rs1642785 in intron 2 (c.74+38 G>C).