Biophysical and Structural Characterisation of Nucleic Acid Complexes with Modified Cyclodextrins Using Circular Dichroism

O’Mahony, Aoife; Cronin, Michael F.; Mcmahon, Anthony; Evans, James; Darcy, Raphael; O’Driscoll, Caitriona M.

doi:10.1002/jps.23922

Cited by 12 publications

(11 citation statements)

References 54 publications

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“…These CD spectral features indicate the typical, helical A‐form of this oligomer in solution . With the addition of surfactants, as in the systems containing the DNA duplex, one can observe the gradual disappearance of the CD signal, implying destabilization of the base stacking of RNA . In the case of IMI_Gly_n2_C12, for samples with p / n >3, a CD signal at a magnitude of the noise level was observed, which is in good agreement with the electrophoresis findings.…”

Section: Resultssupporting

confidence: 84%

“…The pure reference RNA solution is characterized by a rather intense minimum at 211 nm and a weak maximum at 224 nm, followed by a weak minimum at 238 nm and then a dominant positive peak at 260–280 nm. These CD spectral features indicate the typical, helical A‐form of this oligomer in solution . With the addition of surfactants, as in the systems containing the DNA duplex, one can observe the gradual disappearance of the CD signal, implying destabilization of the base stacking of RNA .…”

Section: Resultsmentioning

confidence: 89%

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Dicationic Surfactants with Glycine Counter Ions for Oligonucleotide Transportation

2016

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Gemini surfactants are good candidates to bind, protect, and deliver nucleic acids. Herein, the concept of amino acids (namely glycine) as counter ions of gemini surfactants for gene therapy application was explored. This study was conducted on DNA and RNA oligomers and two quaternary bis-imidazolium salts, having 2,5-dioxahexane and 2,8-dioxanonane spacer groups. The toxicity level of surfactants was assessed by an MTT assay, and their ability to bind nucleic acids was tested through electrophoresis. The nucleic acid conformation was established based on circular dichroism and infrared spectroscopic analyses. The structures of the formed complexes were characterized by small-angle scattering of synchrotron radiation. Both studied surfactants appear to be suitable for gene therapy; however, although they vary by only three methylene groups in the spacer, they differ in binding ability and toxicity. The tested oligonucleotides maintained their native conformations upon surfactant addition and the studied lipoplexes formed a variety of structures. In systems based on a 2,5-dioxahexane spacer, a hexagonal phase was observed for DNA-surfactant complexes and a micellar phase was dominant with RNA. For the surfactant with a 2,8-dioxanonane spacer group, the primitive cubic phase prevailed.

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Section: Resultssupporting

confidence: 84%

Section: Resultsmentioning

confidence: 89%

Dicationic Surfactants with Glycine Counter Ions for Oligonucleotide Transportation

2016

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“…Most likely, the interaction between nucleic acid and gemini surfactant did not disturb the overall conformation of DNA, and the DNA’s structural integrity was retained. The observed alterations of the CD spectra originated from the modification of the DNA arrangement, such as the number of base pairs per helix and/or base angle relative to the helix axis [ 49 ] caused by changes in the hydration level and the condensation process of the nucleic acid chain [ 44 ]. A slightly different situation was visible in the case of C16 surfactant ( Fig 6d ), for which the negative ellipticity increased with increasing surfactant content and over p/n = 4, the CD spectra remained unaltered.…”

Section: Resultsmentioning

confidence: 99%

Gemini Surfactants Based on Bis-Imidazolium Alkoxy Derivatives as Effective Agents for Delivery of Nucleic Acids: A Structural and Spectroscopic Study

et al. 2015

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The success rate of gene therapy depends on the efficient transfection of genetic material into cells. The golden mean between harmlessness and high effectiveness can be provided by synthetic lipid-like molecules that are similar to the components of biological membranes. Cationic gemini surfactants are one such moiety and because of their favourable physicochemical properties (double positive electric charge, reduced toxicity, low values of critical micelle concentration), they show great potential as delivery system components for genetic material in gene therapy. The aim of this study was to investigate the process of the complexation of cationic gemini surfactants with nucleic acids: double-stranded DNA of different sizes (21 bp, ~185 bp, ~20 kbp) and siRNA (21 bp). The tested series of dicationic surfactants consists of bis-imidazolium quaternary salts with varying lengths of hydrophobic side chains (m = 5, 6, 7, 8, 9, 11, 12, 14, 16). On the basis of the data obtained by circular dichroism spectroscopy and electrophoresis, we concluded that the studied gemini surfactants with long side chains effectively bind nucleic acids at low concentrations, which leads to the formation of stable lipoplexes. Images obtained by atomic force microscopy also confirmed the formation of vesicular structures, i.e., complexes between DNA and surfactants. The cytotoxicity of selected surfactants was also tested on HeLa cells. The surfactant toxicity significantly depends on surfactant geometry (the length of hydrophobic chain).

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“…Thus, ellipticity changes measured at the band centered at l = 275 nm for increasing concentrationso f1 or the 1:2e and 1:2h complexes in the presence of ac onstant concentrationo fD NA (1.23 10 À5 mol L À1 )s howed nearly linear decreases significantly larger for the gemini-type complexes than for 1 ( Figure 6B). At the largest 1/DNA molarr atios, ellipticitiesb ecome even slightly negative for the 1:2e and 1:2h dimericcomplexes,which is attributed to the full condensation of DNA, [54][55][56] butn ot in the case of the monomeric species 1.…”

Section: Dna Complexation and Cdplexc Haracterizationmentioning

confidence: 94%

Host–Guest‐Mediated DNA Templation of Polycationic Supramolecules for Hierarchical Nanocondensation and the Delivery of Gene Material

Gallego‐Yerga

Blanco‐Fernández

Urbiola

et al. 2015

Chemistry A European J

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Only a few examples of monodisperse molecular entities that can compact exogenous nucleic acids into nanocomplexes, protect the cargo from the biological environment, facilitate cell internalization, and promote safe transfection have been reported up to date. Although these species open new venues for fundamental studies on the structural requirements that govern the intervening processes and their application in nonviral gene-vector design, the synthesis of these moieties generally requires a relatively sophisticated chemistry, which hampers further development in gene therapy. Herein, we report an original strategy for the reversible complexation and delivery of DNA based on the supramolecular preorganization of a β-cyclodextrin-scaffolded polycationic cluster facilitated by bisadamantane guests. The resulting gemini-type, dual-cluster supramolecules can then undergo DNA-templated self-assembly at neutral pH value by bridging parallel DNA oligonucleotide fragments. This hierarchical DNA condensation mechanism affords transfectious nanoparticles with buffering capabilities, thus facilitating endosomal escape following cell internalization. Protonation also destabilizes the supramolecular dimers and consequently the whole supramolecular edifice, thus assisting DNA release. Our advanced hypotheses are supported by isothermal titration calorimetry, NMR and circular dichroism spectroscopic analysis, gel electrophoresis, dynamic light scattering, TEM, molecular mechanics, molecular dynamics, and transfection studies conducted in vitro and in vivo.

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Biophysical and Structural Characterisation of Nucleic Acid Complexes with Modified Cyclodextrins Using Circular Dichroism

Cited by 12 publications

References 54 publications

Dicationic Surfactants with Glycine Counter Ions for Oligonucleotide Transportation

Dicationic Surfactants with Glycine Counter Ions for Oligonucleotide Transportation

Gemini Surfactants Based on Bis-Imidazolium Alkoxy Derivatives as Effective Agents for Delivery of Nucleic Acids: A Structural and Spectroscopic Study

Host–Guest‐Mediated DNA Templation of Polycationic Supramolecules for Hierarchical Nanocondensation and the Delivery of Gene Material

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