Search results for "G-quadruplexe"
showing 10 items of 68 documents
Comparative biological evaluation and G-quadruplex interaction studies of two new families of organometallic gold(I) complexes featuring N-heterocycl…
2020
Experimental organometallic gold(I) compounds hold promise for anticancer therapy. This study reports the synthesis of two novel families of gold(I) complexes, including N1-substituted bis-N-heterocyclic carbene (NHC) complexes of general formula [Au(N1-TBM) 2]BF 4 (N1-TBM = N1-substituted 9-methyltheobromin-8-ylidene) and mixed gold(I) NHC-alkynyl complexes, [Au(N1-TBM)alkynyl]. The compounds were fully characterised for their structure and stability in aqueous environment and in the presence of N-acetyl cysteine by nuclear magnetic resonance (NMR) spectroscopy. The structures of bis(1-ethyl-3,7,9-trimethylxanthin-8-ylidene)gold(I), (4-ethynylpyridine)(1,9-dimethyltheobromine-8-ylidene)gol…
Forever Young: Structural Stability of Telomeric Guanine Quadruplexes in the Presence of Oxidative DNA Lesions**
2021
International audience; Human telomeric DNA, in G-quadruplex (G4) conformation, is characterized by a remarkable structural stability that confers it the capacity to resist to oxidative stress producing one or even clustered 8-oxoguanine (8oxoG) lesions. We present a combined experimental/computational investigation, by using circular dichroism in aqueous solutions, cellular immunofluorescence assays and molecular dynamics simulations, that identifies the crucial role of the stability of G4s to oxidative lesions, related also to their biological role as inhibitors of telomerase, an enzyme overexpressed in most cancers associated to oxidative stress.
How to untie G-quadruplex knots and why?
2021
International audience; For over two decades, the prime objective of the chemical biology community studying G-quadruplexes (G4s) has been to use chemicals to interact with and stabilize G4s in cells to obtain mechanistic interpretations. This strategy has been undoubtedly successful, as demonstrated by recent advances. However, these insights have also led to a fundamental rethinking of G4-targeting strategies: due to the prevalence of G4s in the human genome, transcriptome, and ncRNAome (collectively referred to as the G4ome), and their involvement in human diseases, should we continue developing G4-stabilizing ligands or should we invest in designing molecular tools to unfold G4s? Here, …
Small-molecule affinity capture of DNA/RNA quadruplexes and their identification in vitro and in vivo through the G4RP protocol
2019
International audience; Guanine-rich DNA and RNA sequences can fold into higher-order structures known as G-quadruplexes (or G4-DNA and G4-RNA, respectively). The prevalence of the G4 landscapes in the human genome, transcriptome and ncRNAome (non-coding RNA), collectively known as G4ome, is strongly suggestive of biological relevance at multiple levels (gene expression , replication). Small-molecules can be used to track G4s in living cells for the functional characterization of G4s in both normal and disease-associated changes in cell biology. Here, we describe biotinylated biomimetic ligands referred to as Bio-TASQ and their use as molecular tools that allow for isolating G4s through aff…
Never Cared for What They Do: High Structural Stability of Guanine-Quadruplexes in the Presence of Strand-Break Damage
2022
DNA integrity is an important factor that assures genome stability and, more generally, the viability of cells and organisms. In the presence of DNA damage, the normal cell cycle is perturbed when cells activate their repair processes. Although efficient, the repair system is not always able to ensure complete restoration of gene integrity. In these cases, mutations not only may occur, but the accumulation of lesions can either lead to carcinogenesis or reach a threshold that induces apoptosis and programmed cell death. Among the different types of DNA lesions, strand breaks produced by ionizing radiation are the most toxic due to the inherent difficultly of repair, which may lead to genomi…
TWJ-Screen: an isothermal screening assay to assess ligand/DNA junction interactions in vitro
2017
International audience; The quest for chemicals able to operate at selected genomic loci in a spatiotemporally controlled manner is desirable to create manageable DNA damages. Mounting evidence now shows that alternative DNA structures, including G-quadruplexes and branched DNA (or DNA junctions), might hamper proper progression of replication fork, thus triggering DNA damages and genomic instability. Therefore, small molecules that stabilize these DNA structures are currently scrutinized as a promising way to create genomic defects that cannot be dealt with properly by cancer cells. While much emphasis has been recently given to G-quadruplexes and related ligands, we report herein on three…
Insights into how nucleotide supplements enhance the peroxidase-mimicking DNAzyme activity of the G-quadruplex/hemin system
2012
Since the initial discovery of the catalytic capability of short DNA fragments, this peculiar enzyme-like property (termed DNAzyme) has continued to garner much interest in the scientific community because of the virtually unlimited applications in developing new molecular devices. Alongside the exponential rise in the number of DNAzyme applications in the last past years, the search for convenient ways to improve its overall efficiency has only started to emerge. Credence has been lent to this strategy by the recent demonstration that the quadruplex-based DNAzyme proficiency can be enhanced by ATP supplements. Herein, we have made a further leap along this path, trying first of all to deci…
Microscopic interactions between ivermectin and key human and viral proteins involved in SARS-CoV-2 infection
2021
The identification of chemical compounds able to bind specific sites of the human/viral proteins involved in the SARS-CoV-2 infection cycle is a prerequisite to design effective antiviral drugs. Here we conduct a molecular dynamics study with the aim to assess the interactions of ivermectin, an antiparasitic drug with broad-spectrum antiviral activity, with the human Angiotensin-Converting Enzyme 2 (ACE2), the viral 3CLpro and PLpro proteases, and the viral SARS Unique Domain (SUD). The drug/target interactions have been characterized in silico by describing the nature of the non-covalent interactions found and by measuring the extent of their time duration along the MD simulation. Results …
SELECTIVE G-QUADRUPLEX STABILIZERS: SALPHEN-LIKE COMPLEXES WITH ANTIPROLIFERATIVE ACTIVITY
2013
Schiff base complexes derived from N,N!-bridged tetradentate ligands involving N2O2 donor atoms present very favourable features to act as G4 binders. Thus, a series of square-planar and square pyramidal metal complexes, ML2+ (M = Ni, Cu, and Zn), have been synthesized and characterized.
Template-Assembled Synthetic G-Quartets (TASQ) hydrosolubles : du ligand de quadruplexes d'ADN et d'ARN à la plateforme catalytique
2013
Natural G-quartets, a cyclic and coplanar array of four guanine residues held together via Hoogsteen H-bond network, have recently received much attention due to their involvement in G-quadruplex-DNA, an alternative higher-order DNA structure strongly suspected to play important roles in key cellular events (chromosomal stability, regulation of gene expression). Besides this, synthetic G-quartets, which artificially mimic native G-quartets, have also been widely studied for their involvement in nanotechnological applications (i.e. nanowires, artificial ion channels, etc.). In contrast, intramolecular synthetic G-quartets, also named template-assembled synthetic G-quartet (TASQ), have been m…