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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>","DOI":"10.1002\/chem.202301181","type":"journal-article","created":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T10:05:22Z","timestamp":1682676322000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Structural Perspective into the Interaction of an Oncogenesis\u2010Relevant pre\u2010miRNA G\u2010Quadruplex Ligand Carrier with the Protein Nucleolin"],"prefix":"10.1002","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4620-0174","authenticated-orcid":false,"given":"Tiago","family":"Santos","sequence":"first","affiliation":[{"name":"CICS-UBI \u2013 Health Sciences Research Centre University of Beira Interior  Av. Infante D. 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