Search results for "Quadruplex"

Double chained naphthalenes as G4 binders

2014

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…

Studio dell'interazione di DNA con complessi di metalli di transizione

2014

How Proximal Nucleobases Regulate the Catalytic Activity of G-Quadruplex/Hemin DNAzymes

2018

International audience; G-quadruplexes (G4s) are versatile catalytic DNAs when combined with hemin. Despite the repertoire of catalytically competent G4/hemin complexes studied so far, little is known about the detailed catalytic mechanism of these biocatalysts. Herein, we have carried out an in-depth analysis of the hemin binding site within the G4/hemin catalysts, providing the porphyrinic cofactor with a controlled nucleotidic environment. We intensively assessed the position-dependent catalytic enhancement in model reactions and found that proximal nucleobases enhance the catalytic ability of the G4/hemin complexes. Our results allow for revisiting the mechanism of the G4/hemin-based ca…

Identification and prevention of genotyping errors caused by G-quadruplex- and i-motif-like sequences.

2009

Abstract Background: Reliable PCR amplification of DNA fragments is the prerequisite for most genetic assays. We investigated the impact of G-quadruplex– or i-motif–like sequences on the reliability of PCR-based genetic analyses. Methods: We found the sequence context of a common intronic polymorphism in the MEN1 gene (multiple endocrine neoplasia I) to be the cause of systematic genotyping errors by inducing preferential amplification of one allelic variant [allele dropout (ADO)]. Bioinformatic analyses and pyrosequencing-based allele quantification enabled the identification of the underlying DNA structures. Results: We showed that G-quadruplex– or i-motif–like sequences can reproducibly …

Closer to nature: an ATP-driven bioinspired catalytic oxidation process

2013

The capability of DNA to acquire enzyme-like properties has led to the emergence of the so-called DNAzyme field; herein, we take a further leap along this nature-inspired road, demonstrating that a template assembled synthetic G-quartet (TASQ) can act as a pre-catalyst for catalytic peroxidase-mimicking oxidation reactions, whatever its nature (guanine or guanosine-based G-quartets), in an ATP-dependent manner, thereby bringing this bioinspired TASQzyme process even closer to nature.

The catalytic properties of DNA G-quadruplexes rely on their structural integrity

2021

International audience; The influence of the G-quartet structural integrity on the catalytic activity of the G-quadruplex (G4) was investigated by comparing the G4-DNAzyme performances of a series of G4s with a G-vacancy site and a G-triplex (G-tri). The results presented herein not only confirm that the structural integrity of the 3’-end G-quartet is necessary for G4s to be catalytically competent but also show how to remediate G-vacancy-mediated catalytic activity losses via the addition of guanine surrogates in an approach referred to as G-vacancy complementation strategy that is applicable to parallel G4s only. Furthermore, this study demonstrates that the terminal G-quartet could act a…

An oxidatively damaged G-quadruplex/hemin DNAzyme.

2020

International audience; Oxidative damage of guanine to 8-oxoguanine triggers a partial and variable loss of G-quadruplex/hemin DNAzyme activity and provides clues to the mechanistic origins of DNAzyme deactivation, which originates from an interplay between decreased G-quadruplex stability, lower hemin affinity and a modification of the nature of hemin binding sites.

Ruthenium-arene complexes bearing naphthyl-substituted 1,3-dioxoindan-2-carboxamides ligands for G-quadruplex DNA recognition.

2019

Quadruplex nucleic acids – DNA/RNA secondary structures formed in guanine rich sequences – proved to have key roles in the biology of cancers and, as such, in recent years they emerged as promising targets for small molecules. Many reports demonstrated that metal complexes can effectively stabilize quadruplex structures, promoting telomerase inhibition, downregulation of the expression of cancer-related genes and ultimately cancer cell death. Although extensively explored as anticancer agents, studies on the ability of ruthenium arene complexes to interact with quadruplex nucleic acids are surprisingly almost unknown. Herein, we report on the synthesis and characterization of four novel Ru(…

G-quadruplex recognition by DARPIns through epitope/paratope analogy

2022

AbstractWe investigated the mechanisms leading to the specific recognition of Guanine Guadruplex (G4) by DARPins peptides, which can lead to the design of G4s specific sensors. To this end we carried out all-atom molecular dynamic simulations to unravel the interactions between specific nucleic acids, including human-telomeric (h-telo), Bcl-2, and c-Myc, with different peptides, forming a DARPin/G4 complex. By comparing the sequences of DARPin with that of a peptide known for its high affinity for c-Myc, we show that the recognition cannot be ascribed to sequence similarity but, instead, depends on the complementarity between the three-dimensional arrangement of the molecular fragments invo…