Unraveling the binding characteristics of small ligands to telomeric DNA by pressure modulation

Oliva, Rosario; Mukherjee, Sumitava; Winter, Roland

doi:10.1038/s41598-021-89215-2

Cited by 14 publications

(19 citation statements)

References 59 publications

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“…The small E rel values at high temperatures indicate the single-stranded (unfolded) conformation. Oliva et al [45] measured E rel = 0.33 for the unfolded Htel, which was shorter than our oligos. Their E rel value for the folded hybrid form was a bit higher than our values, but HepB1 was proven to form a hybrid structure in presence of potassium ion.…”

Section: Temperature Stability Of Hepb1-3 Detected By Fretcontrasting

confidence: 58%

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Pressure Perturbation Studies of Noncanonical Viral Nucleic Acid Structures

Somkuti

Molnár

Grád

et al. 2021

Biology

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G-quadruplexes are noncanonical structures formed by guanine-rich sequences of the genome. They are found in crucial loci of the human genome, they take part in the regulation of important processes like cell proliferation and cell death. Much less is known about the subjects of this work, the viral G-quadruplexes. We have chosen three potentially G-quadruplex-forming sequences of hepatitis B. We measured the stability and the thermodynamic parameters of these quadruplexes. We also investigated the potential stabilization of these G-quadruplexes by binding a special ligand that was originally developed for cancer therapy. Fluorescence and infrared spectroscopic measurements were performed over wide temperature and pressure ranges. Our experiments indicate the small unfolding volume change of all three oligos. We found a difference between the unfolding of the 2-quartet and the 3-quartet G-quadruplexes. All three G-quadruplexes were stabilized by TMPyP4, which is a cationic porphyrin developed for stabilizing the human telomere.

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Section: Temperature Stability Of Hepb1-3 Detected By Fretcontrasting

confidence: 58%

“…This means the loss of the energy transfer, i.e., the high intensity of the donor fluorophore is a clear sign of the unfolding of the GQ structure. The folded state can be characterized by the relative FRET efficiency (E rel ) [45]. It is defined as:…”

Section: Temperature Stability Of Hepb1-3 Detected By Fretmentioning

confidence: 99%

Pressure Perturbation Studies of Noncanonical Viral Nucleic Acid Structures

Somkuti

Molnár

Grád

et al. 2021

Biology

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“…A negative band is present at ~260 nm, followed by a band at 245 nm. These spectral features are indicative of a quadruplex adopting an antiparallel conformation [ 31 , 33 ]. Upon berberine binding, the general spectral features of 22AG remain the same, indicating that the conformation of 22AG is still antiparallel.…”

Section: Resultsmentioning

confidence: 99%

Binding Properties of RNA Quadruplex of SARS-CoV-2 to Berberine Compared to Telomeric DNA Quadruplex

Oliva

Mukherjee

Manisegaran

et al. 2022

IJMS

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Previous studies suggest that berberine, an isoquinoline alkaloid, has antiviral potential and is a possible therapeutic candidate against SARS-CoV-2. The molecular underpinnings of its action are still unknown. Potential targets include quadruplexes (G4Q) in the viral genome as they play a key role in modulating the biological activity of viruses. While several DNA-G4Q structures and their binding properties have been elucidated, RNA-G4Qs such as RG-1 of the N-gene of SARS-CoV-2 are less explored. Using biophysical techniques, the berberine binding thermodynamics and the associated conformational and hydration changes of RG-1 could be characterized and compared with human telomeric DNA-G4Q 22AG. Berberine can interact with both quadruplexes. Substantial changes were observed in the interaction of berberine with 22AG and RG-1, which adopt different topologies that can also change upon ligand binding. The strength of interaction and the thermodynamic signatures were found to dependent not only on the initial conformation of the quadruplex, but also on the type of salt present in solution. Since berberine has shown promise as a G-quadruplex stabilizer that can modulate viral gene expression, this study may also contribute to the development of optimized ligands that can discriminate between binding to DNA and RNA G-quadruplexes.

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“…In previous studies, it was reported that ThT has the ability to bind to several nucleic acid molecules, such as G-quadruplexes, DNAs, and RNAs [ 34 , 35 , 40 ]. ThT was also found to bind specifically to tRNA [ 34 ].…”

Section: Resultsmentioning

confidence: 99%

“…ThT emission is characterized by a very low quantum yield when it is free in solution [ 40 ]. Upon binding to nucleic acids, a strong increase of the fluorescence quantum yield is observed, which depends on the targeted structure.…”

Section: Resultsmentioning

confidence: 99%

Ions in the Deep Subsurface of Earth, Mars, and Icy Moons: Their Effects in Combination with Temperature and Pressure on tRNA–Ligand Binding

Jahmidi-Azizi

Gault

Cockell

et al. 2021

IJMS

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The interactions of ligands with nucleic acids are central to numerous reactions in the biological cell. How such reactions are affected by harsh environmental conditions such as low temperatures, high pressures, and high concentrations of destructive ions is still largely unknown. To elucidate the ions’ role in shaping habitability in extraterrestrial environments and the deep subsurface of Earth with respect to fundamental biochemical processes, we investigated the effect of selected salts (MgCl2, MgSO4, and Mg(ClO4)2) and high hydrostatic pressure (relevant for the subsurface of that planet) on the complex formation between tRNA and the ligand ThT. The results show that Mg2+ salts reduce the binding tendency of ThT to tRNA. This effect is largely due to the interaction of ThT with the salt anions, which leads to a strong decrease in the activity of the ligand. However, at mM concentrations, binding is still favored. The ions alter the thermodynamics of binding, rendering complex formation that is more entropy driven. Remarkably, the pressure favors ligand binding regardless of the type of salt. Although the binding constant is reduced, the harsh conditions in the subsurface of Earth, Mars, and icy moons do not necessarily preclude nucleic acid–ligand interactions of the type studied here.

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Unraveling the binding characteristics of small ligands to telomeric DNA by pressure modulation

Cited by 14 publications

References 59 publications

Pressure Perturbation Studies of Noncanonical Viral Nucleic Acid Structures

Pressure Perturbation Studies of Noncanonical Viral Nucleic Acid Structures

Binding Properties of RNA Quadruplex of SARS-CoV-2 to Berberine Compared to Telomeric DNA Quadruplex

Ions in the Deep Subsurface of Earth, Mars, and Icy Moons: Their Effects in Combination with Temperature and Pressure on tRNA–Ligand Binding

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