Anomeric DNA quadruplexes

Kolganova, Natalia A.; Varizhuk, Anna M.; Новиков, Роман А.; Florentiev, V. L.; Pozmogova, Galina E.; Borisova, O. F.; Shchyolkina, Anna K.; Smirnov, Igor P.; Kaluzhny, Dmitry N.; Timofeev, Edward N.

doi:10.4161/adna.28422

Cited by 13 publications

(8 citation statements)

References 41 publications

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“…A modification to the loop nucleotides in TBA may result in significantly higher nuclease resistance for the modified aptamer. For example, extraordinary nuclease resistance has been reported for anomeric modification of TBA in loop regions 23 . An increase in nuclease resistance may potentially affect the results of clotting time tests due to slower degradation of the modified TBA variants in blood plasma.…”

Section: Resultsmentioning

confidence: 99%

A Universal Base in a Specific Role: Tuning up a Thrombin Aptamer with 5-Nitroindole

Цветков

Varizhuk

Pozmogova

et al. 2015

Sci Rep

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In this study we describe new modified analogs of the thrombin binding aptamer (TBA) containing 5-nitroindole residues. It has been shown that all modified TBAs form an anti-parallel G-quadruplex structure and retain the ability to inhibit thrombin. The most advanced TBA variant (TBA-N8) has a substantially increased clotting time and two-fold lower IC50 value compared to the unmodified prototype. Molecular modelling studies suggest that the improved anticoagulant properties of TBA-N8 result from changes in the binding mode of the analog. A modified central loop in TBA-N8 is presumed to participate in the binding of the target protein. Studies of FAM labelled TBA and TBA-N8 showed an improved binding affinity of the modified aptamer and provided evidence of a direct interaction between the modified central loop and thrombin. Our findings have implications for the design of new aptamers with improved binding affinities.

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Section: Resultsmentioning

confidence: 99%

A Universal Base in a Specific Role: Tuning up a Thrombin Aptamer with 5-Nitroindole

Цветков

Varizhuk

Pozmogova

et al. 2015

Sci Rep

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“…An equally important feature, which facilitates the determination of the aptamer utility in the treatment of human diseases, is G4 thermodynamic stability. Improvement in this area was possible by the introduction of 2′-deoxy-8-bromoguanosine [44], 2′-deoxy-5-fluorouridine [38], 2′-deoxy-2′-fluoro-D-arabinonucleoside [46], unlocked nucleic acid monomer [39,40], 4-thiouridine [40], 2′,3′-seco-4-thiouridine [40], 2′-C-piperazino-unlocked nucleic acid monomer [49], 5′-5′ inversion of polarity sites [50,51], 5-bromo-2′-deoxyuridine [52], a C3 spacer [43], and anomeric α-nucleotides [53]. The most significant inconvenience of the therapeutic use of TBA is its high susceptibility to nuclease degradation in a biological environment.…”

Section: Anticoagulant Agentsmentioning

confidence: 99%

“…The most significant inconvenience of the therapeutic use of TBA is its high susceptibility to nuclease degradation in a biological environment. This problem can be solved inter alia by the inversion of polarity sites at the terminal sequence [54], covalent ligation of the 5′ and 3′ ends of TBA [55], or the introduction of anomeric α-nucleotides [53].…”

Section: Anticoagulant Agentsmentioning

confidence: 99%

G-Quadruplex-Forming Aptamers—Characteristics, Applications, and Perspectives

2019

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G-quadruplexes constitute a unique class of nucleic acid structures formed by G-rich oligonucleotides of DNA- or RNA-type. Depending on their chemical nature, loops length, and localization in the sequence or structure molecularity, G-quadruplexes are highly polymorphic structures showing various folding topologies. They may be formed in the human genome where they are believed to play a pivotal role in the regulation of multiple biological processes such as replication, transcription, and translation. Thus, natural G-quadruplex structures became prospective targets for disease treatment. The fast development of systematic evolution of ligands by exponential enrichment (SELEX) technologies provided a number of G-rich aptamers revealing the potential of G-quadruplex structures as a promising molecular tool targeted toward various biologically important ligands. Because of their high stability, increased cellular uptake, ease of chemical modification, minor production costs, and convenient storage, G-rich aptamers became interesting therapeutic and diagnostic alternatives to antibodies. In this review, we describe the recent advances in the development of G-quadruplex based aptamers by focusing on the therapeutic and diagnostic potential of this exceptional class of nucleic acid structures.

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“…The anticoagulant properties of the chimeric aptamers were retained only with intact TT loops. On the contrary, modification of the TGT loop only substantially increased the nuclease resistance of the chimeric aptamer without notable disturbance of its anticoagulant activity [ 178 ].…”

Section: Stabilization or Destabilization Of A Gq By The Same Syntmentioning

confidence: 99%

In What Ways Do Synthetic Nucleotides and Natural Base Lesions Alter the Structural Stability of G-Quadruplex Nucleic Acids?

Sági¹

2017

Journal of Nucleic Acids

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Synthetic analogs of natural nucleotides have long been utilized for structural studies of canonical and noncanonical nucleic acids, including the extensively investigated polymorphic G-quadruplexes (GQs). Dependence on the sequence and nucleotide modifications of the folding landscape of GQs has been reviewed by several recent studies. Here, an overview is compiled on the thermodynamic stability of the modified GQ folds and on how the stereochemical preferences of more than 70 synthetic and natural derivatives of nucleotides substituting for natural ones determine the stability as well as the conformation. Groups of nucleotide analogs only stabilize or only destabilize the GQ, while the majority of analogs alter the GQ stability in both ways. This depends on the preferred syn or anti N-glycosidic linkage of the modified building blocks, the position of substitution, and the folding architecture of the native GQ. Natural base lesions and epigenetic modifications of GQs explored so far also stabilize or destabilize the GQ assemblies. Learning the effect of synthetic nucleotide analogs on the stability of GQs can assist in engineering a required stable GQ topology, and exploring the in vitro action of the single and clustered natural base damage on GQ architectures may provide indications for the cellular events.

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Anomeric DNA quadruplexes

Cited by 13 publications

References 41 publications

A Universal Base in a Specific Role: Tuning up a Thrombin Aptamer with 5-Nitroindole

A Universal Base in a Specific Role: Tuning up a Thrombin Aptamer with 5-Nitroindole

G-Quadruplex-Forming Aptamers—Characteristics, Applications, and Perspectives

In What Ways Do Synthetic Nucleotides and Natural Base Lesions Alter the Structural Stability of G-Quadruplex Nucleic Acids?

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