Journal ArticleDOI
Looking for efficient G-quadruplex ligands: evidence for selective stabilizing properties and telomere damage by drug-like molecules.
Bruno Pagano,Jussara Amato,Nunzia Iaccarino,Chiara Cingolani,Pasquale Zizza,Annamaria Biroccio,Ettore Novellino,Antonio Randazzo +7 more
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TLDR
Interestingly, two of the investigated ligands showed selective G‐quadruplex‐stabilizing properties and biological activity, which may represent useful leads for the development of more potent and selective ligands.Abstract:
There is currently significant interest in the development of G-quadruplex-interactive compounds, given the relationship between the ability to stabilize these non-canonical DNA structures and anticancer activity. In this study, a set of biophysical assays was applied to evaluate the binding of six drug-like ligands to DNA G-quadruplexes with different folding topologies. Interestingly, two of the investigated ligands showed selective G-quadruplex-stabilizing properties and biological activity. These compounds may represent useful leads for the development of more potent and selective ligands.read more
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G4‐associated human diseases
TL;DR: Advances are focused on, which further dispel the view that genomic biology is limited to the confines of the canonical B‐form DNA duplex, and show how quadruplexes contribute spatial and temporal dimensionalities to linear sequence information.
Journal ArticleDOI
Conjugating a groove-binding motif to an Ir(III) complex for the enhancement of G-quadruplex probe behavior
Modi Wang,Zhifeng Mao,Tian-Shu Kang,Chun-Yuen Wong,Jean-Louis Mergny,Jean-Louis Mergny,Chung-Hang Leung,Dik-Lung Ma +7 more
TL;DR: G-quadruplex groove binder benzo[d,e]isoquinoline was linked to a Ir(iii) complex to generate a highly selective DNA probe.
Journal ArticleDOI
Water-Soluble Ruthenium(II) Complexes with Chiral 4-(2,3-Dihydroxypropyl)-formamide Oxoaporphine (FOA): In Vitro and in Vivo Anticancer Activity by Stabilization of G-Quadruplex DNA, Inhibition of Telomerase Activity, and Induction of Tumor Cell Apoptosis
TL;DR: Mechanistic insights indicate that 6 displays low toxicity and can be a novel anticancer drug candidate.
Journal ArticleDOI
Ligand binding to telomeric G-quadruplex DNA investigated by funnel-metadynamics simulations
Federica Moraca,Jussara Amato,Francesco Ortuso,Anna Artese,Bruno Pagano,Ettore Novellino,Stefano Alcaro,Michele Parrinello,Michele Parrinello,Vittorio Limongelli,Vittorio Limongelli +10 more
TL;DR: FM simulations have elucidated the binding mechanism of the anticancer alkaloid berberine to the human telomeric G4 and computed a quantitatively well-characterized free-energy landscape that allows identifying two low-energy ligand binding modes and the presence of higher energy prebinding states.
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G-Quadruplexes at Telomeres: Friend or Foe?
TL;DR: There is some evidence that G-quadruplexes at telomeres may play a protective capping role, at least in yeast, and that they may positively affect telomere maintenance by either the enzyme telomerase or by recombination-based mechanisms.
References
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AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility
Garrett M. Morris,Ruth Huey,William Lindstrom,Michel F. Sanner,Richard K. Belew,David S. Goodsell,Arthur J. Olson +6 more
TL;DR: AutoDock4 incorporates limited flexibility in the receptor and its utility in analysis of covalently bound ligands is reported, using both a grid‐based docking method and a modification of the flexible sidechain technique.
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Telomeres shorten during ageing of human fibroblasts.
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Water Suppression That Works. Excitation Sculpting Using Arbitrary Wave-Forms and Pulsed-Field Gradients
Tsang-Lin Hwang,A.J Shaka +1 more
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Quantitative visualization of DNA G-quadruplex structures in human cells
TL;DR: It is shown explicitly that G-quadruplex formation in DNA is modulated during cell-cycle progression and that endogenous G- quadruplex DNA structures can be stabilized by a small-molecule ligand and corroborate the application of stabilizing ligands in a cellular context to target G- Quadruplexes and intervene with their function.
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Targeting G-quadruplexes in gene promoters: a novel anticancer strategy?
TL;DR: The evidence for G-quadruplexes in gene promoters is described and their potential as therapeutic targets are discussed, as well as progress in the development of strategies to harness this potential through intervention with small-molecule ligands.