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DC Field | Value | Language |
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dc.contributor.author | Mazzini, Stefania | - |
dc.contributor.author | Gargallo Gómez, Raimundo | - |
dc.contributor.author | Musso, Loana | - |
dc.contributor.author | De Santis, Francesca | - |
dc.contributor.author | Aviñó Andrés, Anna | - |
dc.contributor.author | Scaglioni, Leonardo | - |
dc.contributor.author | Eritja i Casadellà, Ramon | - |
dc.contributor.author | Di Nicola, Massimo | - |
dc.contributor.author | Zunino, Franco | - |
dc.contributor.author | Amatulli, Annabella | - |
dc.contributor.author | Dallavalle, Sabrina | - |
dc.date.accessioned | 2019-10-10T10:51:26Z | - |
dc.date.available | 2019-10-10T10:51:26Z | - |
dc.date.issued | 2019-10-04 | - |
dc.identifier.issn | 1661-6596 | - |
dc.identifier.uri | http://hdl.handle.net/2445/142066 | - |
dc.description.abstract | The stabilization of G-quadruplex DNA structures by small molecules with affinity to oncogene promoters has emerged as a promising anticancer strategy, due to a potential role in gene expression regulation. We explored the ability of BMH-21 (1) and its analogue BA-41 (2) to bind the G-quadruplex structure present in the c-KIT promoter by biophysical methods and molecular modeling. We provide evidence that both compounds interact with the c-KIT 21-mer sequence. The stable monomeric intramolecular parallel G-quadruplex obtained by the mutation of positions 12 and 21 allowed the precise determination of the binding mode by NMR and molecular dynamics studies. Both compounds form a complex characterized by one ligand molecule positioned over the tetrad at the 30-end, stabilized by an extensive network of pi-pi interactions. The binding constants (Kb) obtained with fluorescence are similar for both complexes (around 10^6 M-1). Compound BA-41 (2) showed significant antiproliferative activity against a human lymphoma cell line, SU-DHL4, known to express substantial levels of c-KIT. However, the partial inhibition of c-KIT expression by Western blot analysis suggested that the interaction of compound 2 with the c-KIT promoter is not the primary event and that multiple e ects provide a contribution as determinants of biological activity. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | MDPI | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.3390/ijms20194927 | - |
dc.relation.ispartof | International Journal of Molecular Sciences, 2019, vol. 20, num. 19, p. 4927 | - |
dc.relation.uri | https://doi.org/10.3390/ijms20194927 | - |
dc.rights | cc-by (c) Mazzini, Stefania et al., 2019 | - |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es | - |
dc.source | Articles publicats en revistes (Enginyeria Química i Química Analítica) | - |
dc.subject.classification | Ressonància magnètica nuclear | - |
dc.subject.classification | G-estructures | - |
dc.subject.other | Nuclear magnetic resonance | - |
dc.subject.other | G-structures | - |
dc.title | Stabilization of c-KIT G-Quadruplex DNA structures by the RNA polymerase I inhibitors BMH-21 and BA-41 | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 691964 | - |
dc.date.updated | 2019-10-10T10:51:26Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 31590335 | - |
Appears in Collections: | Articles publicats en revistes (Enginyeria Química i Química Analítica) |
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691964.pdf | 4.01 MB | Adobe PDF | View/Open |
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