Molecular Modelling and Investigation of Bioactive Stable DNA G-Quadruplex d(G4T4G4) under Different Physiological Conditions using Molecular Dynamics Simulation DOI Open Access
Jitendra Prajapati, Ramesh Kumar Yadav, Umesh Yadava

et al.

Prabha Materials Science Letters, Journal Year: 2024, Volume and Issue: 4(1), P. 107 - 118

Published: Dec. 27, 2024

We are reporting a molecular dynamics study on the structure and conformation of DNA quadruplex. The single molecule quadruplex's coordinates were obtained modeled using PDB ID 1d59. simulation's sequence is d(GGGGTTTTGGGG). In beginning, two hairpin structures constructed with loops holding thymine residues at either end, forming four-stranded helical structure. cyclic hydrogen bonds created by kept guanine all four strands in one plane. was subjected to simulation for 100ns periodic intervals 10ns, dynamical pathway's trajectory examined. deviations fluctuations viz. RMSD, RMSF Rg plots analyzed, shape time-evolved outcome compared crystal Our findings reveal few peculiar properties which we have discussed this paper. helix axis torsion angle parameters calculated. results interpretation give idea about quadruplex interaction external agents inspire do further research telomeric regions living chromosomes.

Language: Английский

Structural Unfolding of G-Quadruplexes: From Small Molecules to Antisense Strategies DOI Creative Commons

Giorgia Fracchioni,

Sabrina Vailati,

Marta Grazioli

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(15), P. 3488 - 3488

Published: July 25, 2024

G-quadruplexes (G4s) are non-canonical nucleic acid secondary structures that have gathered significant interest in medicinal chemistry over the past two decades due to their unique structural features and potential roles a variety of biological processes disorders. Traditionally, research efforts focused on stabilizing G4s, while recent years, attention has progressively shifted G4 destabilization, unveiling new therapeutic perspectives. This review provides an in-depth overview advances development small molecules, starting with controversial role TMPyP4. Moreover, we described effective metal complexes addition G4-disrupting molecules as well good ligands can destabilize G4s response external stimuli. Finally, presented antisense strategies promising approach for destabilizing particular focus 2'-OMe oligonucleotide, peptide acid, locked acid. Overall, this emphasizes importance understanding dynamics ongoing develop selective G4-unfolding modulate function potential.

Language: Английский

Citations

8
ESCMID's World Antimicrobial Resistance Awareness Week 2024: Key Takeaways and Path Forward DOI Creative Commons

Tomislav Meštrović,

Giorgia Caruana, Christian Kraef

et al.

CMI Communications, Journal Year: 2025, Volume and Issue: unknown, P. 105071 - 105071

Published: March 1, 2025

Language: Английский

Citations

0
Dibenzoacridinium Derivatives as a New Class of G-Quadruplex Ligands with Antiviral Properties DOI

Amani Kabbara,

Corinne Buré,

Aurore Guédin

et al.

Published: Jan. 1, 2025

Language: Английский

Citations

0
Targeting Mycobacterium tuberculosis Parallel G-Quadruplex Motifs with Aminoglycosides Neomycin and Streptomycin: Spectroscopic and Calorimetric Aspects DOI
Anupama Rai, Niki S. Jha

The Journal of Physical Chemistry B, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 4, 2025

Mycobacterium tuberculosis (Mtb) contains potential G-quadruplex (PGQ) motifs in the genes espK and cyp51, which are crucial for bacteria's virulence within host cells. Aminoglycoside molecules commonly used as antibiotics ribosomal targets. This study provides insight into interactions between these aminoglycosides Mtb-PGQ sequences (espK cyp51), shedding light on structural thermodynamic dynamics of their binding. demonstrates stability, affinity, conformation presence neomycin streptomycin. Ultraviolet-visible spectroscopy (UV–vis), circular dichroism (CD), CD thermal melting, isothermal titration calorimetry (ITC), fluorescence intercalator displacement (FID) assays were to comprehensively examine interactions. Our results reveal that with Mtb-PGQexhibits hypochromism accompanied by a 4–5 nm red shift UV–visible absorption titration, whereas streptomycin exhibits hypochromic without changes maximum wavelength. Notably, shows nonlinear binding isotherm, suggesting involvement more than one process formation neomycin.Mtb-PGQ complexes. Scatchard plot analysis indicates higher affinity values compared weaker studies decreases ellipticity while retaining parallel topology, ultimately enhancing stability both cyp51. In contrast, destabilizes ITC reveals strongest relative order being NEO-cyp51 > NEO-espk STR-cyp51 STR-espk. Moreover, possesses unique dual mode through grooves well stacking. FID further confirm lower DC50 value streptomycin, is strong displacer thiazole orange. Thus, show amino groups selectively recognizes cyp51 over espK.

Language: Английский

Citations

0
Oligostyrylbenzene Derivatives with Antiparasitic and Antibacterial Activity as Potent G-Quadruplex Ligands DOI Creative Commons
Manuel Pérez-Soto, Pablo Peñalver,

Paloma Muñoz-Báez

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(24), P. 5875 - 5875

Published: Dec. 12, 2024

G-quadruplexes (G4s) are non-canonical secondary structures that play a crucial role in the regulation of genetic expression. This study explores interaction between G4s and small family oligostyrylbenzene (OSB) derivatives, characterized by tris(styryl)benzene tetrastyrylbenzene backbones, functionalized with either trimethylammonium or 1-methylpyridinium groups. Initially identified as DNA ligands, these OSB derivatives have now been recognized potent G4 binders, surpassing binding affinity commercially available ligands such pyridostatin displaying good selectivity for over duplex DNA. Furthermore, 1 2 demonstrated significant antiparasitic activity against bloodstream forms T. brucei extracellular L. major, high indices when compared to MRC-5 healthy control cells. Derivatives exhibited moderate biocidal effects range Gram-positive Gram-negative bacterial strains. Notably, synergistic antibacterial effect was observed compounds were combined traditional antibiotics, particularly Acinetobacter baumannii, highlighting their potential utility addressing drug-resistant infections. The differences bioactivity among can be attributed variations cellular uptake, proved flow cytometry analysis. suggests degree internalization plays pivotal efficacy.

Language: Английский

Citations

1
Molecular Modelling and Investigation of Bioactive Stable DNA G-Quadruplex d(G4T4G4) under Different Physiological Conditions using Molecular Dynamics Simulation DOI Open Access
Jitendra Prajapati, Ramesh Kumar Yadav, Umesh Yadava

et al.

Prabha Materials Science Letters, Journal Year: 2024, Volume and Issue: 4(1), P. 107 - 118

Published: Dec. 27, 2024

We are reporting a molecular dynamics study on the structure and conformation of DNA quadruplex. The single molecule quadruplex's coordinates were obtained modeled using PDB ID 1d59. simulation's sequence is d(GGGGTTTTGGGG). In beginning, two hairpin structures constructed with loops holding thymine residues at either end, forming four-stranded helical structure. cyclic hydrogen bonds created by kept guanine all four strands in one plane. was subjected to simulation for 100ns periodic intervals 10ns, dynamical pathway's trajectory examined. deviations fluctuations viz. RMSD, RMSF Rg plots analyzed, shape time-evolved outcome compared crystal Our findings reveal few peculiar properties which we have discussed this paper. helix axis torsion angle parameters calculated. results interpretation give idea about quadruplex interaction external agents inspire do further research telomeric regions living chromosomes.

Language: Английский

Citations

0