Search results for "G-quadruplexes"

Exploring the Reactivity and Biological Effects of Heteroleptic N-Heterocyclic Carbene Gold(I)- Alkynyl Complexes

2020

With the aim to explore the effects of different organometallic ligands on the reactivity and biological properties of a series of twelve heteroleptic AuI complexes, of general formula [Au(NHC)(alkynyl)] (NHC = benzimidazolylidene or 1,3-dihydroimidazolylidene) were synthesized and characterized by 1H and 13C NMR and elemental analysis, and in some cases also by X-ray diffraction. The compounds were all stable in H2O/DMSO as established by NMR spectroscopy, while they could react with model thiols (EtSH) in the presence of water to undergo ligand-substitution reactions. 1H NMR experiments showed that dissociation of the more labile alkynyl ligand was possible for all compounds, while in the…

DESIGN, SYNTHESIS, AND BIOLOGICAL EVALUATION OF NOVEL HETEROCYCLIC DERIVATIVES AS MODULATORS OF B-DNA AND G-QUADRUPLEXES DNA FUNCTIONS

Development of Polyamine‐Substituted Triphenylamine Ligands with High Affinity and Selectivity for G‐Quadruplex DNA

2019

Currently, significant efforts are devoted to designing small molecules able to bind selectively to guanine quadruplexes (G4s). These noncanonical DNA structures are implicated in various important biological processes and have been identified as potential targets for drug development. Previously, a series of triphenylamine (TPA)-based compounds, including macrocyclic polyamines, that displayed high affinity towards G4 DNA were reported. Following this initial work, herein a series of second-generation compounds, in which the central TPA has been functionalised with flexible and adaptive linear polyamines, are presented with the aim of maximising the selectivity towards G4 DNA. The acid-bas…

A Thermophilic Tetramolecular G-Quadruplex/Hemin DNAzyme.

2017

International audience; The quadruplex-based DNAzyme system is one of the most useful artificial enzymes or catalysts; their unique properties make them reliable alternatives to proteins for performing catalytic transformation. The first prototype of a thermally stable DNAzyme system is presented. This thermophilic DNAzyme is capable of oxidizing substrates at high temperatures (up to 95 degrees C) and long reaction times (up to 18 h at 75 degrees C). The catalytic activity of the DNAzymes were investigated with the standard peroxidase-mimicking oxidation of 2,2'-azino-bis(3-ethylbenzothiozoline-6-sulfonic acid) (ABTS) by H2O2. The step-by-step design of this unique heat-activated G-quadrup…

Transcriptome-wide identification of transient RNA G-quadruplexes in human cells

2018

Guanine-rich RNA sequences can fold into four-stranded structures, termed G-quadruplexes (G4-RNAs), whose biological roles are poorly understood, and in vivo existence is debated. To profile biologically relevant G4-RNA in the human transcriptome, we report here on G4RP-seq, which combines G4-RNA-specific precipitation (G4RP) with sequencing. This protocol comprises a chemical crosslinking step, followed by affinity capture with the G4-specific small-molecule ligand/probe BioTASQ, and target identification by sequencing, allowing for capturing global snapshots of transiently folded G4-RNAs. We detect widespread G4-RNA targets within the transcriptome, indicative of transient G4 formation in…

Discovery of new G-quadruplex binding chemotypes

2013

We report here on the discovery and preliminary evaluation of a novel non-macrocyclic low molecular weight quadruplex-stabilizing chemotype. The lead compounds, based on a furan core, show high G-quadruplex stabilisation and selectivity as well as potent in vitro anti-proliferative activity.

The interaction of Schiff Base complexes of nickel(II) and zinc(II) with duplex and G-quadruplex DNA

2017

The duplex and G-quadruplex DNA-binding of six nickel(II) and zinc(II) complexes of three salphen-like ligands (salphen = N,N?-bis-salicylidene-1,2-phenylenediaminato) was investigated by UV-visible absorption and circular dichroism spectroscopy. The results obtained, in particular the values of the DNA-binding constants, Kb, point out that the nickel(II) complexes show a higher affinity toward both duplex and G-quadruplex DNA, compared to the analogous zinc(II) complexes. Interestingly, the zinc(II) complexes possess high selectivity toward G-quadruplex DNA, being negligible their binding with duplex DNA. Molecular dynamics (MD) simulations provided atomistic models for the interpretation …

Spectroscopic and electrochemical study of interactions between DNA and different salts of 1,4-dihydropyridine AV-153

2020

1,4-dihydropyridines (1,4-DHP) possess important biochemical and pharmacological properties, including antimutagenic and DNA-binding activity. The latter activity was first described for water-soluble 1,4-DHP with carboxylic group in position 4, the sodium salt of the 1,4-DHP derivative AV-153 among others. Some data show the modification of physicochemical properties and biological activities of organic compounds by metal ions that form the salts. We demonstrated the different affinity to DNA and DNA-protecting capacity of AV-153 salts, depending on the salt-forming ion (Na, K, Li, Rb, Ca, Mg). This study aimed to use different approaches to collate data on the DNA-binding mode of AV-153-N…

Tight DNA-protein complexes isolated from barley seedlings are rich in potential guanine quadruplex sequences

2020

Background The concept of chromatin domains attached to the nuclear matrix is being revisited, with nucleus described as a set of topologically associating domains. The significance of the tightly bound to DNA proteins (TBP), a protein group that remains attached to DNA after its deproteinization should be also revisited, as the existence of these interactions is in good agreement with the concept of the topologically associating domain. The work aimed to characterize the DNA component of TBP isolated from barley seedlings. Methods The tight DNA-protein complexes from the first leaves, coleoptiles, and roots of barley seedlings were isolated by purification with chromatography on nitrocell…

Combined spectroscopic and theoretical analysis of the binding of a water-soluble perylene diimide to DNA/RNA polynucleotides and G-quadruplexes.

2021

We present here a combined spectroscopic and theoretical analysis of the binding of N,N’-bis(2-(1-piperazino)ethyl)-3,4,9,10-perylenetetracarboxylic acid diimide dichloride (PZPERY) to different biosubstrates. Absorbance titrations and circular dichroism experiments, melting studies and isothermal calorimetry (ITC) titrations reveal a picture where the binding to natural double-stranded DNA is very different from that to double and triple-stranded RNAs (poly(A)∙poly(U) and poly(U)∙poly(A)⁎poly(U)). As confirmed also by the structural and energetic details clarified by density functional theory (DFT) calculations, intercalation occurs for DNA, with a process driven by the combination of aggr…