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  1. AU="Zofia Gdaniec"
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  1. Article ; Online: Thermodynamic and structural contributions of the 6-thioguanosine residue to helical properties of RNA

    Michał Gładysz / Witold Andrałojć / Tomasz Czapik / Zofia Gdaniec / Ryszard Kierzek

    Scientific Reports, Vol 9, Iss 1, Pp 1-

    2019  Volume 8

    Abstract: Abstract Thionucleotides, especially 4-thiouridine and 6-thioguanosine, are photosensitive molecules that photocrosslink to both proteins and nucleic acids, and this feature is a major reason for their application in various investigations. To get ... ...

    Abstract Abstract Thionucleotides, especially 4-thiouridine and 6-thioguanosine, are photosensitive molecules that photocrosslink to both proteins and nucleic acids, and this feature is a major reason for their application in various investigations. To get insight into the thermodynamic and structural contributions of 6-thioguanosine to the properties of RNA duplexes a systematic study was performed. In a series of RNA duplexes, selected guanosine residues located in G-C base pairs, mismatches (G-G, G-U, and G-A), or 5′ and 3′-dangling ends were replaced with 6-thioguanosine. Generally, the presence of 6-thioguanosine diminishes the thermodynamic stability of RNA duplexes. This effect depends on its position within duplexes and the sequence of adjacent base pairs. However, when placed at a dangling end a 6-thioguanosine residue actually exerts a weak stabilizing effect. Furthermore, the structural effect of 6-thioguanosine substitution appears to be minimal based on NMR and Circular Dichroism (CD) data.
    Keywords Medicine ; R ; Science ; Q
    Subject code 612
    Language English
    Publishing date 2019-03-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Formation of an RNA Quadruplex-Duplex Hybrid in Living Cells Between mRNA of the Epidermal Growth Factor Receptor (EGFR) and a G-Rich Antisense Oligoribonucleotide

    Dorota Gudanis / Damian Kaniowski / Katarzyna Kulik / Daniel Baranowski / Zofia Gdaniec / Barbara Nawrot

    Cells, Vol 9, Iss 2375, p

    2020  Volume 2375

    Abstract: Antisense DNA oligonucleotides, short interfering RNAs (siRNAs), and CRISPR/Cas9 genetic tools are the most useful therapeutic nucleic acids regulating gene expression based on the antisense specificity towards messenger RNA. Here, we present an ... ...

    Abstract Antisense DNA oligonucleotides, short interfering RNAs (siRNAs), and CRISPR/Cas9 genetic tools are the most useful therapeutic nucleic acids regulating gene expression based on the antisense specificity towards messenger RNA. Here, we present an effective novel strategy for inhibiting translation based on the antisense-controlled formation of an RNA quadruplex-duplex hybrid (QDH) between a G-rich RNA antisense oligoribonucleotide (Q-ASO) and specific mRNA, comprising two distant G-tracts. We selected epidermal growth factor receptor (EGFR) as a well-established target protein in anticancer therapy. The chemically modified, bi-functional anti-EGFR Q-ASO and a 56-nt long EGFR mRNA fragment, in the presence of potassium ions, were shown to form in vitro very stable parallel G-quadruplex containing a 28-nt long external loop folding to two duplex-stem structure. Besides, the Q-ASOs effectively reduced EGFR mRNA levels compared to the non-modified RNA and DNA antisense oligonucleotides (rASO, dASO). In addition, the hybridization specificity of Q-ASO comprising a covalently attached fluorescent tag was confirmed in living cells by visualization of the G4 green fluorescent species in the presence of other antisense inhibitors under competitive conditions. The results presented here offer novel insights into the potential application of Q-ASOs for the detection and/or alteration of (patho)biological processes through RNA:RNA quadruplex-duplex formation in cellular systems.
    Keywords G-quadruplex ; quadruplex-duplex hybrid ; RNA G-rich antisense oligonucleotide ; EGFR mRNA ; selective G4 fluorescent probe ; oBMVC derivative ; Biology (General) ; QH301-705.5
    Subject code 612
    Language English
    Publishing date 2020-10-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
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  3. Article ; Online: Computational and NMR studies of RNA duplexes with an internal pseudouridine-adenosine base pair

    Indrajit Deb / Łukasz Popenda / Joanna Sarzyńska / Magdalena Małgowska / Ansuman Lahiri / Zofia Gdaniec / Ryszard Kierzek

    Scientific Reports, Vol 9, Iss 1, Pp 1-

    2019  Volume 13

    Abstract: Abstract Pseudouridine (Ψ) is the most common chemical modification present in RNA. In general, Ψ increases the thermodynamic stability of RNA. However, the degree of stabilization depends on the sequence and structural context. To explain experimentally ...

    Abstract Abstract Pseudouridine (Ψ) is the most common chemical modification present in RNA. In general, Ψ increases the thermodynamic stability of RNA. However, the degree of stabilization depends on the sequence and structural context. To explain experimentally observed sequence dependence of the effect of Ψ on the thermodynamic stability of RNA duplexes, we investigated the structure, dynamics and hydration of RNA duplexes with an internal Ψ-A base pair in different nearest-neighbor sequence contexts. The structures of two RNA duplexes containing 5′-GΨC/3′-CAG and 5′-CΨG/3′-GAC motifs were determined using NMR spectroscopy. To gain insight into the effect of Ψ on duplex dynamics and hydration, we performed molecular dynamics (MD) simulations of RNA duplexes with 5′-GΨC/3′-CAG, 5′-CΨG/3′-GAC, 5′-AΨU/3′-UAA and 5′-UΨA/3′-AAU motifs and their unmodified counterparts. Our results showed a subtle impact from Ψ modification on the structure and dynamics of the RNA duplexes studied. The MD simulations confirmed the change in hydration pattern when U is replaced with Ψ. Quantum chemical calculations showed that the replacement of U with Ψ affected the intrinsic stacking energies at the base pair steps depending on the sequence context. The calculated intrinsic stacking energies help to explain the experimentally observed sequence dependent changes in the duplex stability from Ψ modification.
    Keywords Medicine ; R ; Science ; Q
    Subject code 612
    Language English
    Publishing date 2019-11-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
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  4. Article ; Online: Novel Short PEG Chain-Substituted Porphyrins

    Dawid Lazewski / Malgorzata Kucinska / Edward Potapskiy / Joanna Kuzminska / Artur Tezyk / Lukasz Popenda / Stefan Jurga / Anna Teubert / Zofia Gdaniec / Jacek Kujawski / Katarzyna Grzyb / Tomasz Pedzinski / Marek Murias / Marcin Wierzchowski

    International Journal of Molecular Sciences, Vol 23, Iss 10029, p

    Synthesis, Photochemistry, and In Vitro Photodynamic Activity against Cancer Cells

    2022  Volume 10029

    Abstract: This work presents the synthesis and characterization of metal-free, zinc (II), and cobalt (II) porphyrins substituted with short PEG chains. The synthesized compounds were characterized by UV-Vis, 1 H and 13 C NMR spectroscopy, and MALDI-TOF mass ... ...

    Abstract This work presents the synthesis and characterization of metal-free, zinc (II), and cobalt (II) porphyrins substituted with short PEG chains. The synthesized compounds were characterized by UV-Vis, 1 H and 13 C NMR spectroscopy, and MALDI-TOF mass spectrometry. The origin of the absorption bands for tested compounds in the UV-Vis range was determined using a computational model based on the electron density functional theory (DFT) and its time-dependent variant (TD-DFT). The photosensitizing activity was evaluated by measuring the ability to generate singlet oxygen (ΦΔ), which reached values up to 0.54. The photodynamic activity was tested using bladder (5637), prostate (LNCaP), and melanoma (A375) cancer cell lines. In vitro experiments clearly showed the structure–activity relationship regarding types of substituents, their positions in the phenyl ring, and the variety of central metal ions on the porphyrin core. Notably, the metal-free derivative 3 and its zinc derivative 6 exerted strong cytotoxic activity toward 5637 cells, with IC 50 values of 8 and 15 nM, respectively. None of the tested compounds induced a cytotoxic effect without irradiation. In conclusion, these results highlight the potential value of the tested compounds for PDT application.
    Keywords porphyrins ; photodynamic therapy ; polyethylene glycol ; singlet oxygen ; cancer cells ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 540
    Language English
    Publishing date 2022-09-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Metal-cation regulation of enzyme dynamics is a key factor influencing the activity of S-adenosyl-l-homocysteine hydrolase from Pseudomonas aeruginosa

    Justyna Czyrko / Joanna Sliwiak / Barbara Imiolczyk / Zofia Gdaniec / Mariusz Jaskolski / Krzysztof Brzezinski

    Scientific Reports, Vol 8, Iss 1, Pp 1-

    2018  Volume 15

    Abstract: Abstract S-adenosyl-l-homocysteine hydrolase from Pseudomonas aeruginosa (PaSAHase) coordinates one K+ ion and one Zn2+ ion in the substrate binding area. The cations affect the enzymatic activity and substrate binding but the molecular mechanisms of ... ...

    Abstract Abstract S-adenosyl-l-homocysteine hydrolase from Pseudomonas aeruginosa (PaSAHase) coordinates one K+ ion and one Zn2+ ion in the substrate binding area. The cations affect the enzymatic activity and substrate binding but the molecular mechanisms of their action are unknown. Enzymatic and isothermal titration calorimetry studies demonstrated that the K+ ions stimulate the highest activity and strongest ligand binding in comparison to other alkali cations, while the Zn2+ ions inhibit the enzyme activity. PaSAHase was crystallized in the presence of adenine nucleosides and K+ or Rb+ ions. The crystal structures show that the alkali ion is coordinated in close proximity of the purine ring and a 23Na NMR study showed that the monovalent cation coordination site is formed upon ligand binding. The cation, bound in the area of a molecular hinge, orders and accurately positions the amide group of Q65 residue to allow its interaction with the ligand. Moreover, binding of potassium is required to enable unique dynamic properties of the enzyme that ensure its maximum catalytic activity. The Zn2+ ion is bound in the area of a molecular gate that regulates access to the active site. Zn2+ coordination switches the gate to a shut state and arrests the enzyme in its closed, inactive conformation.
    Keywords Medicine ; R ; Science ; Q
    Subject code 540
    Language English
    Publishing date 2018-07-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
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  6. Article ; Online: Author Correction

    Shawn M. Lyons / Dorota Gudanis / Steven M. Coyne / Zofia Gdaniec / Pavel Ivanov

    Nature Communications, Vol 8, Iss 1, Pp 1-

    Identification of functional tetramolecular RNA G-quadruplexes derived from transfer RNAs

    2017  Volume 1

    Abstract: The original version of this Article contained an error in the spelling of the author Steven M. Coyne, which was incorrectly given as Stephen M. Coyne. This has now been corrected in both the PDF and HTML versions of the Article. ...

    Abstract The original version of this Article contained an error in the spelling of the author Steven M. Coyne, which was incorrectly given as Stephen M. Coyne. This has now been corrected in both the PDF and HTML versions of the Article.
    Keywords Science ; Q
    Language English
    Publishing date 2017-12-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
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  7. Article ; Online: Identification of functional tetramolecular RNA G-quadruplexes derived from transfer RNAs

    Shawn M. Lyons / Dorota Gudanis / Steven M. Coyne / Zofia Gdaniec / Pavel Ivanov

    Nature Communications, Vol 8, Iss 1, Pp 1-

    2017  Volume 11

    Abstract: RNA G-quadruplexes (RG4) occur in vivo and have regulatory roles in mRNA metabolism. Here the authors show that the guanine residue stretches at the 5’ end of tRNA-derived stress-induced RNAs mediate the formation of tetramolecular RG4 structures, which ... ...

    Abstract RNA G-quadruplexes (RG4) occur in vivo and have regulatory roles in mRNA metabolism. Here the authors show that the guanine residue stretches at the 5’ end of tRNA-derived stress-induced RNAs mediate the formation of tetramolecular RG4 structures, which play a role in the post-transcriptional regulation of gene expression.
    Keywords Science ; Q
    Language English
    Publishing date 2017-10-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Thermodynamic Features of Structural Motifs Formed by β-L-RNA.

    Marta Szabat / Dorota Gudanis / Weronika Kotkowiak / Zofia Gdaniec / Ryszard Kierzek / Anna Pasternak

    PLoS ONE, Vol 11, Iss 2, p e

    2016  Volume 0149478

    Abstract: This is the first report to provide comprehensive thermodynamic and structural data concerning duplex, hairpin, quadruplex and i-motif structures in β-L-RNA series. Herein we confirm that, within the limits of experimental error, the thermodynamic ... ...

    Abstract This is the first report to provide comprehensive thermodynamic and structural data concerning duplex, hairpin, quadruplex and i-motif structures in β-L-RNA series. Herein we confirm that, within the limits of experimental error, the thermodynamic stability of enantiomeric structural motifs is the same as that of naturally occurring D-RNA counterparts. In addition, formation of D-RNA/L-RNA heterochiral duplexes is also observed; however, their thermodynamic stability is significantly reduced in reference to homochiral D-RNA duplexes. The presence of three locked nucleic acid (LNA) residues within the D-RNA strand diminishes the negative effect of the enantiomeric, complementary L-RNA strand in the formation of heterochiral RNA duplexes. Similar behavior is also observed for heterochiral LNA-2'-O-methyl-D-RNA/L-RNA duplexes. The formation of heterochiral duplexes was confirmed by 1H NMR spectroscopy. The CD curves of homochiral L-RNA structural motifs are always reversed, whereas CD curves of heterochiral duplexes present individual features dependent on the composition of chiral strands.
    Keywords Medicine ; R ; Science ; Q
    Subject code 612
    Language English
    Publishing date 2016-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article: Effects of G-quadruplex topology on translational inhibition by tRNA fragments in mammalian and plant systems in vitro

    Jackowiak, Paulina / Anna Hojka-Osinska / Dorota Gudanis / Katarzyna Gasiorek / Marek Figlerowicz / Michal Stelmaszczuk / Zofia Gdaniec

    international journal of biochemistry & cell biology. 2017 Nov., v. 92

    2017  

    Abstract: The folding of tRNA fragments (tRFs) into G-quadruplex structures and the implications of G-quadruplexes in translational inhibition have been studied mainly in mammalian systems. To increase our knowledge of these phenomena, we determined the influence ... ...

    Abstract The folding of tRNA fragments (tRFs) into G-quadruplex structures and the implications of G-quadruplexes in translational inhibition have been studied mainly in mammalian systems. To increase our knowledge of these phenomena, we determined the influence of human and plant tRFs and model G-quadruplexes on translation in rabbit reticulocyte lysate and wheat germ extract. The efficiency of translational inhibition in the mammalian system was strongly associated with the type of G-quadruplex topology. In the plant system, the ability of a small RNA to adopt the G-quadruplex conformation was not sufficient to repress translation, indicating the importance of other structural determinants.
    Keywords humans ; models ; nucleic acid conformation ; rabbits ; topology ; transfer RNA ; translation (genetics) ; wheat germ
    Language English
    Dates of publication 2017-11
    Size p. 148-154.
    Publishing place Elsevier Ltd
    Document type Article
    ZDB-ID 1228429-4
    ISSN 1878-5875 ; 1357-2725
    ISSN (online) 1878-5875
    ISSN 1357-2725
    DOI 10.1016/j.biocel.2017.10.001
    Database NAL-Catalogue (AGRICOLA)

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  10. Article: Polyaminooligonucleotide: NMR structure of duplex DNA containing a nucleoside with spermine residue, N-[4,9,13-triazatridecan-1-yl]-2′-deoxycytidine

    Brzezinska, Jolanta / Lukasz Popenda / Wojciech T. Markiewicz / Zofia Gdaniec

    BBA - General Subjects. 2014 Mar., v. 1840

    2014  

    Abstract: The nature of the polyamine–DNA interactions at a molecular level is not clearly understood.In order to shed light on the binding preferences of polyamine with nucleic acids, the NMR solution structure of the DNA duplex containing covalently bound ... ...

    Abstract The nature of the polyamine–DNA interactions at a molecular level is not clearly understood.In order to shed light on the binding preferences of polyamine with nucleic acids, the NMR solution structure of the DNA duplex containing covalently bound spermine was determined.The structure of 4-N-[4,9,13-triazatridecan-1-yl]-2′-deoxycytidine (dCSp) modified duplex was compared to the structure of the reference duplex. Both duplexes are regular right-handed helices with all attributes of the B-DNA form. The spermine chain which is located in a major groove and points toward the 3′ end of the modified strand does not perturb the DNA structure.In our study the charged polyamine alkyl chain was found to interact with the DNA surface. In the majority of converged structures we identified the presumed hydrogen bonding interactions between O6 and N7 atoms of G4 and the first internal –NH2+− amino group. Additional interaction was found between the second internal –NH2+− amino group and the oxygen atom of the phosphate of C3 residue.The knowledge of the location and nature of a structure-specific binding site for spermine in DNA should be valuable in understanding gene expression and in the design of new therapeutic drugs.
    Keywords B-DNA ; binding sites ; drugs ; gene expression ; hydrogen bonding ; nuclear magnetic resonance spectroscopy ; nucleosides ; oxygen ; phosphates ; spermine
    Language English
    Dates of publication 2014-03
    Size p. 1163-1170.
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 840755-1
    ISSN 0304-4165
    ISSN 0304-4165
    DOI 10.1016/j.bbagen.2013.12.008
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