Article In: cienciavitae

Structural Perspective into the Interaction of an Oncogenesis‐Relevant pre‐miRNA G‐Quadruplex Ligand Carrier with the Protein Nucleolin

Chemistry – A European Journal

Santos T.; Micael S. Silva; Eurico J Cabrita — 2023 — Wiley

Key information

Authors:

Santos T.; Micael S. Silva; Lionel Imbert; Maria P. C. Campello (Maria Paula Cordeiro Crespo Cabral Campello Aboim de Barros); António Paulo; Samir Amrane; Gilmar F. Salgado; Carla Cruz; Eurico J Cabrita

Published in

05/17/2023

Abstract

<jats:title>Abstract</jats:title><jats:p>The structural determinants of the interaction of the G‐quadruplex (G4) motif found in precursor miRNA 149 (rG4) with the acridine orange derivative C<jats:sub>8</jats:sub>, a G4 ligand stabilizer possessing anticancer activity, and the protein nucleolin (overexpressed in cancer cells) were investigated by Nuclear Magnetic Resonance (NMR) spectroscopy. For the rG4/C<jats:sub>8</jats:sub> complex, the results revealed a strong stabilizing interaction between the aromatic core and the iodinated ring of the C<jats:sub>8</jats:sub> ligand with the rG4 structure. The NMR study revealed also different interaction patterns between nucleolin and rG4 and nucleolin and rG4/C<jats:sub>8</jats:sub> complex. In the absence of the ligand, rG4 establishes interactions with polar residues of the protein while for the rG4/C<jats:sub>8</jats:sub> complex, these contacts are mainly established with amino acids that have hydrophobic side chains. However, nucleolin chemical shift perturbation studies in the presence of rG4 or rG4/C<jats:sub>8</jats:sub> reveal the same location between domains 1 and 2 of the protein, which suggests that the rG4 and rG4/C<jats:sub>8</jats:sub> complex bind in this region. This puzzling structural study opens a new framework to study rG4/ligand/nucleolin complexes that might impact the biogenesis of miRNA 149.</jats:p>

Publication details

Authors in the community:

Publication version

AO - Author's Original

Publisher

Wiley

Title of the publication container

Chemistry – A European Journal

Volume

29

Issue

39

ISSN

0947-6539

DOI

10.1002/chem.202301181

Fields of Science and Technology (FOS)

chemical-sciences - Chemical sciences

Publication language (ISO code)

eng - English

Alternative identifier (URI)

https://scholar.tecnico.ulisboa.pt/records/9hueMKKlV7IYmO_Qd9cCSOPN12hOd98mh000

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