Search results for "Quadruplex"

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

2014

“ One Ring to Bind Them All ”—Part I: The Efficiency of the Macrocyclic Scaffold for G-Quadruplex DNA Recognition

2010

International audience; Macrocyclic scaffolds are particularly attractive for designing selective G-quadruplex ligands essentially because, on one hand, they show a poor affinity for the "standard" B-DNA conformation and, on the other hand, they fit nicely with the external G-quartets of quadruplexes. Stimulated by the pioneering studies on the cationic porphyrin TMPyP4 and the natural product telomestatin, follow-up studies have developed, rapidly leading to a large diversity of macrocyclic structures with remarkable-quadruplex binding properties and biological activities. In this review we summarize the current state of the art in detailing the three main categories of quadruplex-binding …

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…

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 …

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—representative of different topologies and possessing biological relevance, such as telomeric or regulatory sequences—have been considered. An original multiscale protocol, making use of molecular dynamics (MD) simulations and quantum mechanics/molecular mechanics (QM/MM) calculations, allowed us to compare the theoretical and experimental circular dichroism spectra of the different DNA topologies, readily providing atomic-level details of the CHE–DNA binding…

"Dynamical Docking" of Cyclic Dinuclear Au(I) Bis-N-heterocyclic Complexes Facilitates Their Binding to G-Quadruplexes.

2022

With the aim to improve the design of metal complexes as stabilizers of noncanonical DNA secondary structures, namely, G-quadruplexes (G4s), a series of cyclic dinuclear Au(I) N-heterocyclic carbene complexes based on xanthine and benzimidazole ligands has been synthesized and characterized by various methods, including X-ray diffraction. Fluorescence resonance energy transfer (FRET) and CD DNA melting assays unraveled the compounds’ stabilization properties toward G4s of different topologies of physiological relevance. Initial structure–activity relationships have been identified and recognize the family of xanthine derivatives as those more selective toward G4s versus duplex DNA. The bind…

Structure and Dynamics of RNA Guanine Quadruplexes in SARS-CoV-2 Genome. Original Strategies against Emerging Viruses

2021

Guanine quadruplex (G4) structures in the 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 modeling and corroborated by the excellent agreement between the corresponding calculated and experimental circular dichroism spectra. We prove the stability of the RG-1 G4 arrangement as well as its interaction with G4 ligands potentially inhibiting viral protein translation.

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…

G-quadruplex vs. duplex-DNA binding of nickel(II) and zinc(II) Schiff base complexes

2016

Novel nickel(II) (1) and zinc(II) (2) complexes of a Salen-like ligand, carrying a pyrimidine ring on the N,N' bridge, were synthesized and characterized. Their interaction with duplex and G-quadruplex DNA was investigated in aqueous solution through UV-visible absorption, circular dichroism and viscometry measurements. The results obtained point out that, while the zinc(II) complex does not interact with both duplex and G-quadruplex DNA, the nickel(II) complex 1 binds preferentially to G-quadruplex respect to duplex-DNA, with values of the DNA-binding constants, Kb, 2.6×10(5)M(-1) and 3.5×10(4)M(-1), respectively. Molecular dynamics simulations provided an atomic level model of the top-sta…

Circular Dichroism of DNA G-Quadruplexes: Combining Modeling and Spectroscopy To Unravel Complex Structures

2016

We report on the comparison between the computational and experimental determination of electronic circular dichroism spectra of different guanine quadruplexes obtained from human telomeric sequences. In particular the difference between parallel, antiparallel, and hybrid structures is evidenced, as well as the induction of transitions between the polymorphs depending on the solution environment. Extensive molecular dynamics simulations (MD) are used to probe the conformational space of the different quadruplexes, and subsequently state-of-the-art hybrid quantum mechanics/molecular mechanics (QM/MM) techniques coupled with excitonic semiempirical Hamiltonian are used to simulate the macromo…