Search results for "Quadruplex"
showing 10 items of 104 documents
NiII, and ZnII Schiff Base Complexes: Telomeric G-quadruplex Stabilizers
2014
Recently, NiII and ZnII metal complexes of the ligand Salpyrim have been synthesized and characterized. Their affinity for wild-type h-Telo G-quadruplex DNA and for calf thymus DNA was investigated by UV absorption spectroscopy, circular dichroism and viscometry. The data collectively suggest that both complexes bind effectively to G-quadruplexes by direct end-stacking, stabilizing the oligonucleotide secondary structure. The two complexes are also typical B-DNA intercalators. Remarkably, their binding constants, Kb, with the G4s structures are about 10 fold higher than those with B-DNA, highlighting the selectivity. Experiments to evaluate the biological activity of the two complexes again…
Characterization of Hydrophilic Gold(I) N-Heterocyclic Carbene (NHC) Complexes as Potent TrxR Inhibitors Using Biochemical and Mass Spectrometric App…
2017
We report here on the synthesis of a series of mono-and dinuclear gold(I) complexes exhibiting sulfonated bis(NHC) ligands and novel hydroxylated mono(NHC) Au(I) compounds, which were also examined for their 'biological activities. Initial cell viability assays show strong antiproliferative activities of the hydroxylated mono(NHC) gold compounds (8 > 9 > 10) against 2008 human ovarian cancer cells even after 1 h incubation. In order to gain insight into the mechanism of biological action of the gold compounds, their effect on the pivotal cellular target seleno-enzyme thioredoxin reductase (TrxR), involved in the maintenance of intracellular redox balance, was investigated in depth. Th…
Identifying and validating the presence of guanine-quadruplexes (G4) within the blood fluke parasite schistosoma mansoni
2021
Schistosomiasis is a neglected tropical disease that currently affects over 250 million individuals worldwide. In the absence of an immunoprophylactic vaccine and the recognition that mono-chemotherapeutic control of schistosomiasis by praziquantel has limitations, new strategies for managing disease burden are urgently needed. A better understanding of schistosome biology could identify previously undocumented areas suitable for the development of novel interventions. Here, for the first time, we detail the presence of G-quadruplexes (G4) and putative quadruplex forming sequences (PQS) within the Schistosoma mansoni genome. We find that G4 are present in both intragenic and intergenic regi…
A Push-Pull Mechanism Helps Design Highly Competent G-Quadruplex-DNA Catalysts
2021
International audience; Massive efforts are currently being invested to improve the performance, versatility, and scope of applications of nucleic acid catalysts. G-quadruplex (G4)/hemin DNAzymes are of particular interest owing to their structural programmability and chemical robustness. However, optimized catalytic efficiency is still bottleneck and the activation mechanism is unclear. Herein, we have designed a series of parallel G4s with different proximal cytosine (dC) derivatives to fine-tune the hemin-binding pocket for G4-DNAzymes. Combining theoretical and experimental methods, we have assessed the dependence of catalytic enhancement on the electronic properties of proximal dCs and…
The noncovalent dimerization of a G-quadruplex/hemin DNAzyme improves its biocatalytic properties.
2020
While many protein enzymes exert their functions through multimerization, which improves both selectivity and activity, this has not yet been demonstrated for other naturally occurring catalysts. Here, we report a multimerization effect applied to catalytic DNAs (or DNAzymes) and demonstrate that the enzymatic efficiency of G-quadruplexes (GQs) in interaction with the hemin cofactor is remarkably enhanced by homodimerization. The resulting non-covalent dimeric GQ–DNAzyme system provides hemin with a structurally defined active site in which both the cofactor (hemin) and the oxidant (H2O2) are activated. This new biocatalytic system efficiently performs peroxidase- and peroxygenase-type biot…
Targeting G-quadruplexes with Organic Dyes: Chelerythrine–DNA Binding Elucidated by Combining Molecular Modeling and Optical Spectroscopy
2019
The DNA-binding of the natural benzophenanthridine alkaloid chelerythrine (CHE) has been assessed by combining molecular modeling and optical absorption spectroscopy. Specifically, both double-helical (B-DNA) and G-quadruplex sequences&mdash
Intragenic G-quadruplex structure formed in the human CD133 and its biological and translational relevance.
2016
Cancer stem cells (CSCs) have been identified in several solid malignancies and are now emerging as a plausible target for drug discovery. Beside the questionable existence of CSCs specific markers, the expression of CD133 was reported to be responsible for conferring CSC aggressiveness. Here, we identified two G-rich sequences localized within the introns 3 and 7 of the CD133 gene able to form G-quadruplex (G4) structures, bound and stabilized by small molecules. We further showed that treatment of patient-derived colon CSCs with G4-interacting agents triggers alternative splicing that dramatically impairs the expression of CD133. Interestingly, this is strongly associated with a loss of C…
Cluster dirhenium(III) cis-dicarboxylates with α-amino acids ligands as mighty selective G4s binders.
2021
The synthesis of four dirhenium(III) cis-dicarboxylates with the α-amino acids residues Asp (I), Glu (II), Phe (III) and Tyr (IV) is presented. The G-quadruplex stabilization potential was evaluated by fluorescence resonance energy transfer - melting analysis. All derivatives show specific binding to c-kit1 quadruplex, while II and IV have also strong stabilization activity to HTelo21 quadruplex. At the same time, the compounds do not show any stabilization activity for ds26 DNA, which suggests unique mechanisms of molecular DNA recognition for these complexes.
Design of guanidinium porphyrins as potential G-quadruplex ligands
2012
We report herein an easy and smooth synthesis of two novel tetra-meso-substituted porphyrins bearing terminal guanidinium functionalities. These two guanidine derivatives are the porphyrin-based analogs of ZnPC , a closely related phthalocyanine-based molecule with four guanidinium arms already reported as an efficient G-quadruplex ligand.
Structure and dynamics of RNA guanine quadruplexes in SARS-CoV-2 genome. Original strategies against emerging viruses
2021
Guanine quadruplexes (G4) structures in viral genome have a key role in modulating viruses’ biological activity. While several DNA G4 structures have been experimentally resolved, RNA G4s are definitely less explored. We report the first calculated G4 structure of the RG-1 RNA sequence of SARS-CoV-2 genome, obtained by using a multiscale approach combining quantum and classical molecular modelling and corroborated by the excellent agreement between the corresponding calculated and experimental circular dichroism spectra. We prove the stability of RG-1 G4 arrangement as well as its interaction with G4 ligands potentially inhibiting viral protein translation.