Search results for "Quadruplex"

Synthesis, characterization and DNA binding studies of potential G4 stabilizer metal complexes

2012

The Interaction of Small Molecules with Biomolecules

2014

The binding of small molecules with biological targets is associated to interesting chemical and biological properties of the resulting supramolecular systems. We have recently reported on the synthesis and characterization of cationic first row transition metal complexes and the study of their DNA binding properties, in aqueous solutions at neutral pH, essentially investigated by viscosimetry and spectroscopic techniques such as circular dichroism, absorption and fluorescence in the UV-visible wavelength range. Of course, such procedure cannot furnish atomic level details of the molecule-DNA interaction. Computational Chemistry may provide support for the interpretation of experimental dat…

Visualization of RNA-Quadruplexes in Live Cells

2015

Visualization of DNA and RNA quadruplex formation in human cells was demonstrated recently with different quadruplex-specific antibodies. Despite the significant interest in these immunodetection approaches, dynamic detection of quadruplex in live cells remains elusive. Here, we report on NaphthoTASQ (N-TASQ), a next-generation quadruplex ligand that acts as a multiphoton turn-on fluorescent probe. Single-step incubation of human and mouse cells with N-TASQ enables the direct detection of RNA-quadruplexes in untreated cells (no fixation, permeabilization or mounting steps), thus offering a unique, unbiased visualization of quadruplexes in live cells.

Molecular recognition of naphthalene diimide ligands by telomeric quadruplex-DNA: the importance of the protonation state and mediated hydrogen bonds.

2016

In depth Monte Carlo conformational scans in combination with molecular dynamics (MD) simulations and electronic structure calculations were applied in order to study the molecular recognition process between tetrasubstituted naphthalene diimide (ND) guests and G-quadruplex (G4) DNA receptors. ND guests are a promising class of telomere stabilizers due to which they are used in novel anticancer therapeutics. Though several ND guests have been studied experimentally in the past, the protonation state under physiological conditions is still unclear. Based on chemical intuition, in the case of N-methyl-piperazine substitution, different protonation states are possible and might play a crucial …

Multitasking Water-Soluble Synthetic G-Quartets: From Preferential RNA-Quadruplex Interaction to Biocatalytic Activity

2013

Natural G-quartets, a cyclic and coplanar array of four guanine res- idues held together through a Watson- Crick/Hoogsteen hydrogen-bond net- work, have received recently much at- tention due to their involvement in G- quadruplex DNA, an alternative higher-order DNA structure strongly suspected to play important roles in key cellular events. Besides this, syn- thetic G-quartets (SQ), which artificial- ly mimic native G-quartets, have also been widely studied for their involve- ment in nanotechnological applications (i.e., nanowires, artificial ion channels, etc.). In contrast, intramolecular syn- thetic G-quartets (iSQ), also named template-assembled synthetic G-quar- tets (TASQ), have been…

Antiproliferative properties and g-quadruplex-binding of symmetrical naphtho[1,2-b:8,7-b’]dithiophene derivatives

2021

Background: G-quadruplex (G4) forming sequences are recurrent in telomeres and promoter regions of several protooncogenes. In normal cells, the transient arrangements of DNA in G-tetrads may regulate replication, transcription, and translation processes. Tumors are characterized by uncontrolled cell growth and tissue invasiveness and some of them are possibly mediated by gene expression involving G-quadruplexes. The stabilization of G-quadruplex sequences with small molecules is considered a promising strategy in anticancer targeted therapy. Methods: Molecular virtual screening allowed us identifying novel symmetric bifunctionalized naphtho[1,2-b:8,7-b’]dithiophene ligands as interesting ca…

Water-soluble isoindolo[2,1-a]quinoxalin-6-imines: In vitro antiproliferative activity and molecular mechanism(s) of action

2015

Abstract Water-soluble isoindoloquinoxalin (IIQ) imines and the corresponding acetates were conveniently prepared from the key intermediates 2-(2′-aminophenyl)-2H-isoindole-1-carbonitriles obtained by a Strecker reaction between substituted 1,2-dicarbaldehydes and 1,2-phenylenediamines. Both series were screened by the National Cancer Institute (Bethesda, MD) and showed potent antiproliferative activity against a panel of 60 human tumor cell lines. Several of the novel compounds showed GI50 values at a nanomolar level on the majority of the tested cell lines. Among IIQ derivatives, methoxy substituents at positions 3 and 8 or/and 9 were especially effective in impairing cell cycle progressi…

Surface-immobilized DNAzyme-type biocatalysis

2014

The structure of the double helix of deoxyribonucleic acid (DNA, also called duplex-DNA) was elucidated sixty years ago by Watson, Crick, Wilkins and Franklin. Since then, DNA has continued to hold a fascination for researchers in diverse fields including medicine and nanobiotechnology. Nature has indeed excelled in diversifying the use of DNA: beyond its canonical role of repository of genetic information, DNA could also act as a nanofactory able to perform some complex catalytic tasks in an enzyme-mimicking manner. The catalytic capability of DNA was termed DNAzyme; in this context, a peculiar DNA structure, a quadruple helix also named quadruplex-DNA, has recently garnered considerable i…

Interplay of three G‑quadruplex units in the KIT promoter

2019

The proto-oncogene KIT encodes for a tyrosine kinase receptor, which is a clinically validated target for treating gastrointestinal stromal tumors. The KIT promoter contains a G-rich domain within a relatively long sequence potentially able to form three adjacent G-quadruplex (G4) units, namely, K2, SP, and K1. These G4 domains have been studied mainly as single quadruplex units derived from short truncated sequences and are currently considered promising targets for anticancer drugs, alternatively to the encoded protein. Nevertheless, the information reported so far does not contemplate the interplay between those neighboring G4s in the context of the whole promoter, possibly thwarting dru…

Deciphering the DNAzyme activity of multimeric quadruplexes: insights into their actual role in the telomerase activity evaluation assay.

2011

The end of human telomeres is comprised of a long G-rich single-stranded DNA (known as 3'-overhang) able to adopt an unusual three-dimensional "beads-on-the-string" organization made of consecutively stacked G-quadruplex units (so-called quadruplex multimers). It has been widely demonstrated that, upon interaction with hemin, discrete quadruplexes acquire peroxidase-mimicking properties, oxidizing several organic probes in H(2)O(2)-rich conditions; this property, known as DNAzyme, has found tens of applications in the last two decades. However, little is known about the DNAzyme activity of multimeric quadruplexes; this is an important question to address, especially in light of recent repor…