Complex formation with protamine prolongs the thrombin-inhibiting effect of DNA aptamer in vivo

Спиридонова, В. А.; Новикова, Т. М.; Nikulina, D.M.; Shishkina, Tatyana; Golubkina, Ekaterina Valerievna; Dyukareva, O.S.; Trizno, N.N.

doi:10.1016/j.biochi.2017.09.010

Cited by 7 publications

(4 citation statements)

References 27 publications

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“…In contrast, the CD spectra of the antiparallel G-quadruplex folding include one maximum near 290 nm and one minimum around 260 nm. It was previously reported that the CD spectrum of RE31 displays a shape that is characteristic for an antiparallel folding topology with two positive CD bands near 245 and 295 nm and one negative signal around 265 nm. , …”

Section: Resultsmentioning

confidence: 99%

“…It was previously reported that the CD spectrum for RE31 displays a shape, which is characteristic for antiparallel folding topology with two positive CD bands near 245 and 295 nm and one negative signal around 265 nm. 17,34 The CD spectra for oligomers O1-O13 containing one or more nucleoside residues in UNA, LNA and β-L-RNA series were recorded to determine the influence of certain modifications on aptamer conformation. All RE31 variants displayed the typical pattern for an antiparallel G-quadruplex structure with two maxima near 245 and 295 nm and one minimum around 265 nm (Figure 2A and 2B).…”

Section: Spectroscopymentioning

confidence: 99%

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Improved RE31 Analogues Containing Modified Nucleic Acid Monomers: Thermodynamic, Structural, and Biological Effects

et al. 2019

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RE31 is a 31-nt DNA aptamer, consisting of the G-quadruplex and a duplex domain, which is able to effectively prolong thrombin time. This article reports on the influence of certain modified nucleotide residues on thermodynamic and biological properties as well as the folding topology of RE31. Particularly, the effect of the presence of canonical nucleosides in unlocked nucleic acid (UNA), locked nucleic acid (LNA) or β-L-RNA series was evaluated. The studies presented herein show that all modified residues can influence G-quadruplex thermal and biological stability in a position dependent manner. The aptamers modified simultaneously with UNA at the T 15 position and LNAs in the duplex part, possess the highest value of melting temperature and a twofold higher anticoagulant effect. Importantly, RE31 variants modified with canonical nucleosides in UNA, LNA or β-L-RNA series exhibit unchanged G-quadruplex folding topology. Crucially, introduction of any of the modified residues into RE31 causes prolongation of aptamer stability in human serum.

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Section: Resultsmentioning

confidence: 99%

Section: Spectroscopymentioning

confidence: 99%

Improved RE31 Analogues Containing Modified Nucleic Acid Monomers: Thermodynamic, Structural, and Biological Effects

et al. 2019

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“…The LNA and UNA residues turned out to have a beneficial influence on RE31 thermal and biological stability with preservation or improvement of its anticoagulant properties [60]. Furthermore, the prolongation of the inhibitory activity of RE31 was possible because of the preparation of DNA-protamine complexes [61].…”

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 results in the rat model showed that PT significantly increased within 2 h after injection of RE31-protamine complexes and remained active for appropriate 6 h, while no noticeable change in clotting time was observed after protamine injections. Thus, the authors conclude that RE31-protamine complexes can prolong the inhibitory activity of the RE31 aptamer [56]. Kotkowiak and his colleagues revealed that all modified residues, unlocked nucleic acid (UNA) (Fig.…”

Section: Re31mentioning

confidence: 97%

Aptamers for Thrombotic Diseases

Li¹,

Zhang²,

Zhao³

et al. 2021

Aptamers for Medical Applications

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Thrombosis is defined as a necessary physiological clotting process of hemostasis or harmful clinical events manifested as acute myocardial infarction (AMI), acute coronary syndromes (ACS), and thrombotic diseases. Nowadays, thrombotic diseases are the leading causes of morbidity and mortality which incur substantial healthcare expenditures worldwide. There are some shortcomings for current antithrombotics including bleeding potential, unpredictable pharmacokinetic and pharmacodynamic profiles, limited reversibility, and so on. Aptamers are short RNA or single-stranded DNA (ssDNA) oligonucleotides that fold into 3D conformations to recognize and bind their cognate targets. Aptamers are selected by an in vitro selection technique, i.e., Systematic Evolution of Ligands by Exponential Enrichment (SELEX). Chemical synthesis renders aptamers both the characteristics of small molecule drugs and those of monoclonal antibodies. Some additional unique features, such as high specificity and affinity, flexible modification and stability, and lack of toxicity and immunogenicity, make aptamers hold great potential as a novel class of drugs and diagnostic reagents. In this review, we focus on the development of several aptamers and in particular those aptamers that have entered into clinical trials against anticoagulation factors and anti-adhesion molecules which are potential antithrombotics for thrombotic diseases.

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Complex formation with protamine prolongs the thrombin-inhibiting effect of DNA aptamer in vivo

Cited by 7 publications

References 27 publications

Improved RE31 Analogues Containing Modified Nucleic Acid Monomers: Thermodynamic, Structural, and Biological Effects

Improved RE31 Analogues Containing Modified Nucleic Acid Monomers: Thermodynamic, Structural, and Biological Effects

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

Aptamers for Thrombotic Diseases

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