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G-Quadruplex Aptamer-Ligand Characterization

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F22%3A00563712" target="_blank" >RIV/68081707:_____/22:00563712 - isvavai.cz</a>

  • Result on the web

    <a href="https://www.mdpi.com/1420-3049/27/20/6781" target="_blank" >https://www.mdpi.com/1420-3049/27/20/6781</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.3390/molecules27206781" target="_blank" >10.3390/molecules27206781</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    G-Quadruplex Aptamer-Ligand Characterization

  • Original language description

    In this work we explore the structure of a G-rich DNA aptamer termed AT11-L2 (TGGTGGTGGTTGTTGTTGGTGGTGGTGGT, derivative of AT11) by evaluating the formation and stability of G-quadruplex (G4) conformation under different experimental conditions such as KCl concentration, temperature, and upon binding with a variety of G4 ligands (360A, BRACO-19, PDS, PhenDC3, TMPyP4). We also determined whether nucleolin (NCL) can be a target of AT11-L2 G4. Firstly, we assessed by circular dichroism, UV and NMR spectroscopies the formation of G4 by AT11-L2. We observed that, for KCl concentrations of 65 mM or less, AT11-L2 adopts hybrid or multiple topologies. In contrast, a parallel topology predominates for buffer containing 100 mM of KCl. The T-m of AT11-L2 in 100 mM of KCl is 38.9 degrees C, proving the weak stability of this sequence. We also found that upon titration with two molar equivalents of 360A, BRACO-19 and PhenDC3, the G4 is strongly stabilized and its topology is maintained, while the addition of 3.5 molar equivalents of TMPyP4 promotes the disruption of G4. The K-D values between AT11-L2 G4, ligands and NCL were obtained by fluorescence titrations and are in the range of mu M for ligand complexes and nM when adding NCL. In silico studies suggest that four ligands bind to the AT11-L2 G4 structure by stacking interactions, while the RBD1,2 domains of NCL interact preferentially with the thymines of AT11-L2 G4. Finally, AT11-L2 G4 co-localized with NCL in NCL-positive tongue squamous cell carcinoma cell line.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    10608 - Biochemistry and molecular biology

Result continuities

  • Project

    <a href="/en/project/EF15_003%2F0000477" target="_blank" >EF15_003/0000477: Structural gymnastics of nucleic acids: from molecular principles through biological functions to therapeutic targets.</a><br>

  • Continuities

    I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Others

  • Publication year

    2022

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    Molecules

  • ISSN

    1420-3049

  • e-ISSN

    1420-3049

  • Volume of the periodical

    27

  • Issue of the periodical within the volume

    20

  • Country of publishing house

    CH - SWITZERLAND

  • Number of pages

    16

  • Pages from-to

    6781

  • UT code for WoS article

    000872819000001

  • EID of the result in the Scopus database

    2-s2.0-85140917571