Doxorubicin binds to duplex RNA with higher affinity than ctDNA and favours the isothermal denaturation of triplex RNA

Rubio, Ana R.; Busto, Natalia; Leal, José M.; Garcı́a, Begoña

doi:10.1039/c6ra21387a

Cited by 9 publications

(7 citation statements)

References 38 publications

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“…Isothermal titration calorimetry 38 NaCl (I = 100 mM, pH 7.0) 0.34 AE 0.06 Fluorescence titration 33 BPES (I = 185 mM, pH 7.0) 0.61 AE 0.06 Isothermal titration calorimetry 9 NaCaC (I = 2.5 mM, pH 7.0) 0.93 AE 0.07 FCS (this work)…”

Section: Methodsmentioning

confidence: 90%

Fluorescence correlation spectroscopy for multiple-site equilibrium binding: a case of doxorubicin–DNA interaction

Zhang

Poniewierski

Sozański

et al. 2019

Phys. Chem. Chem. Phys.

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Section: Methodsmentioning

confidence: 90%

Fluorescence correlation spectroscopy for multiple-site equilibrium binding: a case of doxorubicin–DNA interaction

Zhang

Poniewierski

Sozański

et al. 2019

Phys. Chem. Chem. Phys.

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“…Intensive experimental and theoretical studies have been conducted to investigate the relationship between the biological functions of DOX and its affinity for DNA. On the experimental side, different methodologies have been applied to study the interaction of DOX with the synthetic polynucleotides of the duplex ,, or single-stranded DNA (ssDNA), native DNA, such as calf thymus DNA (ctDNA) , and salmon DNA, the DNA hairpin, , and G-quadruplex DNA , as well as with RNA and tRNA . However, experimental studies alone cannot clearly pinpoint the details of the complicated dynamic behavior of the complex formation or detect how DOX recognizes its specific site in the BP sequence of DNA.…”

Section: Introductionmentioning

confidence: 99%

Thermodynamic Dissection of the Intercalation Binding Process of Doxorubicin to dsDNA with Implications of Ionic and Solvent Effects

et al. 2020

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Doxorubicin (DOX) is a cancer drug that binds to dsDNA through intercalation. A comprehensive microsecond timescale molecular dynamics study is performed for DOX with 16 tetradecamer dsDNA sequences in explicit aqueous solvent, in order to investigate the intercalation process at both binding stages (conformational change and insertion binding stages). The molecular mechanics generalized Born surface area (MM-GBSA) method is adapted to quantify and break down the binding free energy (BFE) into its thermodynamic components, for a variety of different solution conditions as well as different DNA sequences. Our results show that the van der Waals interaction provides the largest contribution to the BFE at each stage of binding. The sequence selectivity depends mainly on the base pairs located downstream from the DOX intercalation site, with a preference for (AT)2 or (TA)2 driven by the favorable electrostatic and/or van der Waals interactions. Invoking the quartet sequence model proved to be most successful to predict the sequence selectivity. Our findings also indicate that the aqueous bathing solution (i.e., water and ions) opposes the formation of the DOX–DNA complex at every binding stage, thus implying that the complexation process preferably occurs at low ionic strength and is crucially dependent on solvent effects.

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“…To form synthetic RNA double helix, poly(A) and poly(U) were mixed 1:1 in buffer (NaCl 0.1 M, NaCac 2.5 mM, pH = 7.0) and let equilibrate overnight in the dark at room temperature to get the double-stranded poly(A)poly(U) (C AU = 2.0 mM in base pairs) [ 65 ]. Similarly, poly(A)poly(U) and poly(U) were mixed 1:1 in the same buffer and left overnight at room temperature to obtain the RNA triple helix (C A2U = 4.0 × 10 −4 M in base triplets) [ 66 ]. A telomeric G-quadruplex structure was prepared by dissolving a 23-residue human telomer (Tel-23: 5′-TAG GGT TAG GGT TAG GGT TAG GG-3′, Sigma-Aldrich, St. Louis, MO, USA) in 50 mM KCl, 2.5 mM NaCac, pH = 6.5.…”

Section: Methodsmentioning

confidence: 99%

On the Different Mode of Action of Au(I)/Ag(I)-NHC Bis-Anthracenyl Complexes Towards Selected Target Biomolecules

et al. 2020

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Gold and silver N-heterocyclic carbenes (NHCs) are emerging for therapeutic applications. Multiple techniques are here used to unveil the mechanistic details of the binding to different biosubstrates of bis(1-(anthracen-9-ylmethyl)-3-ethylimidazol-2-ylidene) silver chloride [Ag(EIA)2]Cl and bis(1-(anthracen-9-ylmethyl)-3-ethylimidazol-2-ylidene) gold chloride [Au(EIA)2]Cl. As the biosubstrates, we tested natural double-stranded DNA, synthetic RNA polynucleotides (single-poly(A), double-poly(A)poly(U) and triple-stranded poly(A)2poly(U)), DNA G-quadruplex structures (G4s), and bovine serum albumin (BSA) protein. Absorbance and fluorescence titrations, mass spectrometry together with melting and viscometry tests show significant differences in the binding features between silver and gold compounds. [Au(EIA)2]Cl covalently binds BSA. It is here evidenced that the selectivity is high: low affinity and external binding for all polynucleotides and G4s are found. Conversely, in the case of [Ag(EIA)2]Cl, the binding to BSA is weak and relies on electrostatic interactions. [Ag(EIA)2]Cl strongly/selectively interacts only with double strands by a mechanism where intercalation plays the major role, but groove binding is also operative. The absence of an interaction with triplexes indicates the major role played by the geometrical constraints to drive the binding mode.

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Doxorubicin binds to duplex RNA with higher affinity than ctDNA and favours the isothermal denaturation of triplex RNA

Abstract: The higher affinity of DOX with AU to give the intercalated complex AU/DOX is responsible for the disproportionation of the groove binding complex, UAU/DOX, to give rise to the AU/DOX and the U/DOX complexes at 25 °C

Cited by 9 publications

References 38 publications

Fluorescence correlation spectroscopy for multiple-site equilibrium binding: a case of doxorubicin–DNA interaction

Fluorescence correlation spectroscopy for multiple-site equilibrium binding: a case of doxorubicin–DNA interaction

Thermodynamic Dissection of the Intercalation Binding Process of Doxorubicin to dsDNA with Implications of Ionic and Solvent Effects

On the Different Mode of Action of Au(I)/Ag(I)-NHC Bis-Anthracenyl Complexes Towards Selected Target Biomolecules

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