A new approach to precise thermodynamic characterization of hybridization properties of modified oligonucleotides: Comparative studies of deoxyribo- and glycine morpholine pentaadenines

Golyshev, Victor M.; Абрамова, Т. В.; Pyshnyi, D. V.; Lomzov, Alexander A.

doi:10.1016/j.bpc.2017.12.004

Cited by 12 publications

(41 citation statements)

References 33 publications

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“…It should have a significant impact on complex formation efficiency in accordance with previous data. 25,57 On the basis of the proposed thermodynamic models, we designed nucleotide sequences of lengthened oligomers as described in section Theoretical analysis. The latter do not form stable hairpins or self-dimers and can efficiently interact with circular complexes.…”

Section: Resultsmentioning

confidence: 99%

“…Concatemer complexes are stabler than the self-limited ones because highly efficient stacking in the nicks stabilizes them. We evaluated this effect in detail for concatemeric 25 and tandem 57 complexes. It is most pronounced for M20/N20 because the lengthened block in M20/N20l disrupts a cooperative interaction in the nick thereby decreasing melting temperature by 6 °C.…”

Section: Resultsmentioning

confidence: 99%

“…Our recent studies showed the possibility of efficient formation of complexes between dA 5 and a dT n oligomer ( n = 10 or higher) or poly(dT). 57 Cooperative interactions in the nicks (coaxial stacking) significantly stabilize tandem complexes. We expect that the presence of a 10 nt dangling end of S10A 5 in a probable complex with the dT n linker of N20T 25 or M20T n should not allow it to engage in stacking interactions efficiently in tandem complexes.…”

Section: Resultsmentioning

confidence: 99%

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Pairing nanoarchitectonics of oligodeoxyribonucleotides with complex diversity: concatemers and self-limited complexes

et al. 2022

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Pairing nanoarchitectonics of oligodeoxyribonucleotides with complex diversity: concatemers and self-limited complexes

et al. 2022

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“…S3). The presence of singular points before and after T 1/2 is another evidence of a two-state transition (''all-or-none'' model) in salt-based diluents, and supports the presence of a unique higher-order structure before T 1/2 , which is different from the stacked coils adopted after the transition [36].…”

Section: Resultsmentioning

confidence: 73%

Characterization of In Vitro G-Quadruplex Formation of Imetelstat Telomerase Inhibitor

Carloni

Wechselberger

Vijlder

2021

Nucleic Acid Therapeutics

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Imetelstat (GRN163L) is a potent and specific telomerase inhibitor currently in clinical development for the treatment of hematological malignancies such as myelofibrosis and myelodysplastic syndrome. It is a 13-mer N3¢-P5¢ thio-phosphoramidate oligonucleotide covalently functionalized at the 5¢-end with a palmitoyl lipid moiety through an aminoglycerol linker. As a competitive inhibitor of human telomerase, imetelstat directly binds to the telomerase RNA component sequence (hTR) in the catalytic site of the enzyme and acts as a direct competitor of human telomere binding. Administration of imetelstat causes progressive shortening of the telomeres, thereby inhibiting malignant cells' proliferation. We report here the ability of imetelstat to form stable, parallel, intermolecular G-quadruplex structures in vitro. The impact of the ionic environment on the formation and stability of imetelstat higher-order structure was investigated through circular dichroism spectroscopy, thermal denaturation analysis, and size-exclusion chromatography. We demonstrated that different structural elements, such as the 5¢-palmitoyl linker and the thio-phosphoramidate backbone, critically contribute to G-quadruplex stability. Experiments further showed that G-quadruplex formation does not hamper binding to the hTR oligonucleotide sequence in vitro.

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“…The T26 does not form intra- and intermolecular structures, and so it was chosen as a model compound to exclude the possible influence of spatial organization features of the ON chain on the efficiency of ON-FD/GNP formation [ 38 ]. Using T26 with a fixed length and nucleotide composition, we were able to investigate the effect of different FDs on the properties of ON-FD/GNPs, including ON adsorption to surface of GNPs.…”

Section: Resultsmentioning

confidence: 99%

Effect of Fluorescent Labels on DNA Affinity for Gold Nanoparticles

et al. 2021

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Fluorophore (FD) labeling is widely used for detection and quantification of various compounds bound to nanocarriers. The systems, composed of gold nanoparticles (GNPs) and oligonucleotides (ONs) labeled with FDs, have wide applications. Our work was aimed at a systemic study of how FD structure (in composition of ON-FDs) influenced the efficiency of their non-covalent associates’ formation with GNPs (ON-FD/GNPs). We examined ONs of different length and nucleotide composition, and corresponding ON-FDs (FDs from a series of xanthene, polymethine dyes; dyes based on polycyclic aromatic hydrocarbons). Methods: fluorometry, dynamic light scattering, high performance liquid chromatography, gel electrophoresis, molecular modeling and methods of thermodynamic and statistical analysis. We observed significant, differing several times, changes in surface density and Langmuir constant values of ON-FDs vs. ONs, evidence for the critical significance of FD nature for binding of ON-FDs with GNPs. Surface density of ON-FD/GNPs; hydrophobicity and total charge of ON or ON-FD; and charge and surface area of FDs were revealed as key factors determining affinity (Langmuir constant) of ON or ON-FDs for GNPs. These factors compose a specific set, which makes possible the highly reliable prediction of efficiency of ONs and ON-FDs binding with GNPs. The principal possibility of creating an algorithm for predictive calculation of efficiency of ONs and GNPs interaction was demonstrated. We proposed a hypothetical model that described the mechanism of contact interaction between negatively charged nano-objects, such as citrate-stabilized GNPs, and ONs or ON-FDs.

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A new approach to precise thermodynamic characterization of hybridization properties of modified oligonucleotides: Comparative studies of deoxyribo- and glycine morpholine pentaadenines

Cited by 12 publications

References 33 publications

Pairing nanoarchitectonics of oligodeoxyribonucleotides with complex diversity: concatemers and self-limited complexes

Pairing nanoarchitectonics of oligodeoxyribonucleotides with complex diversity: concatemers and self-limited complexes

Characterization of In Vitro G-Quadruplex Formation of Imetelstat Telomerase Inhibitor

Effect of Fluorescent Labels on DNA Affinity for Gold Nanoparticles

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