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Molecular Therapy - Nucleic Acids

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Presentation on theme: "Molecular Therapy - Nucleic Acids"— Presentation transcript:

1 Molecular Therapy - Nucleic Acids
Thermodynamic, Anticoagulant, and Antiproliferative Properties of Thrombin Binding Aptamer Containing Novel UNA Derivative  Weronika Kotkowiak, Jolanta Lisowiec-Wachnicka, Jakub Grynda, Ryszard Kierzek, Jesper Wengel, Anna Pasternak  Molecular Therapy - Nucleic Acids  Volume 10, Pages (March 2018) DOI: /j.omtn Copyright © 2017 The Author(s) Terms and Conditions

2 Molecular Therapy - Nucleic Acids 2018 10, 304-316DOI: (10. 1016/j
Molecular Therapy - Nucleic Acids  , DOI: ( /j.omtn ) Copyright © 2017 The Author(s) Terms and Conditions

3 Figure 1 Schematic Representation of TBA and Modified Residues Applied in the Studies Structure of (A) thrombin binding aptamer (TBA), (B) novel 4-thiouracil derivative of UNA, (C) UNA nucleotide monomer, and (D) 4-thiouridine. Molecular Therapy - Nucleic Acids  , DOI: ( /j.omtn ) Copyright © 2017 The Author(s) Terms and Conditions

4 Figure 2 Spectral Analysis of G-quadruplex Folding Topology
Representative circular dichroism spectra (A) and thermal difference spectra (B) of unmodified TBA (black lines) and TBA variants modified with canonical UNA (green lines), UNA-s4U (blue lines), and RNA-s4U (red lines). Molecular Therapy - Nucleic Acids  , DOI: ( /j.omtn ) Copyright © 2017 The Author(s) Terms and Conditions

5 Figure 3 Concentration Dependence of Anticoagulant Effect of Unmodified TBA and TBA Variants Analyzed TBA variants possessed: UNA-s4U at T3 (red triangles), UNA-s4U at T7 (red squares), UNA-s4U at T9 (red circles), UNA-A at T7 (orange squares), UNA-C at T7 (gray squares), UNA-G at T7 (green squares), UNA-C at T9 (gray circles), UNA-A at T3 (orange triangles), and UNA-A at T12 (orange stars). Molecular Therapy - Nucleic Acids  , DOI: ( /j.omtn ) Copyright © 2017 The Author(s) Terms and Conditions

6 Figure 4 The Antiproliferative Activity of Unmodified TBA (Black Bars) and TBA Variants Modified with RNA-s4U at T3, T7, T9, and T13 (Red Bars) or at T3, T7, T9, and T12 (Red Crosshatch Bars) All data are presented as the mean ± SEM from three independent experiments (*p < 0.05, Student’s t test; n = 3). Molecular Therapy - Nucleic Acids  , DOI: ( /j.omtn ) Copyright © 2017 The Author(s) Terms and Conditions


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