2026-04-23T03:28:13Zhttps://riubu.ubu.es/oai/request

oai:riubu.ubu.es:10259/47462022-04-29T12:02:48Zcom_10259_4365com_10259_5086com_10259_2604com_10259_4883col_10259_4366col_10259_4884

Pérez Arnáiz, Cristina 435 500 Busto Vázquez, Natalia 83 500 Santolaya, Javier ac73c679-73ee-420a-b52e-e67a1b6502d7 500 Leal Villalba, José María 314 500 Barone, Giampaolo 2502c306-a514-4e96-9cd8-7a3b547ae347 500 García Ruiz, Begoña 217 500 2018-03-08T09:23:37Z 2019-03-01T03:45:06Z 2018-03 0304-4165 http://hdl.handle.net/10259/4746 10.1016/j.bbagen.2017.10.020 Background: Stabilization of G-quadruplex helices by small ligands has attracted growing attention because they inhibit the activity of the enzyme telomerase, which is overexpressed in> 80% cancer cells. TMPyP4, one of the most studied G-quadruplex ligands, is used as a model to show that the ligands can exhibit different binding features with different conformations of a human telomeric specific sequence. Methods: UV–Vis, FRET melting Assay, Isothermal Titration Calorimetry, Time-resolved Fluorescence lifetime, T-Jump and Molecular Dynamics. Results: TMPyP4 yields two different complexes with two Tel22 telomeric conformations in the presence of Na+ or K+. T-Jump kinetic experiments show that the rates of formation and dissociation of these complexes in the ms time scale differ by one order of magnitude. MD simulations reveal that, in K+ buffer, “hybrid 1” conformation yields kinetic constants on interaction with TMPyP4 one order lower than “hybrid 2”. The binding involves π–π stacking with external loop bases. Conclusions: For the first time we show that for a particular buffer TMPyP4 interacts in a kinetically different way with the two Tel22 conformations even if the complexes formed are thermodynamically indistinguishable. General significance: G-quadruplexes, endowed with technological applications and potential impact on regulation mechanisms, define a new research field. The possibility of building different conformations from same sequence is a complex issue that confers G-quadruplexes very interesting features. The obtaining of reliable kinetic data constitutes an efficient tool to determine reaction mechanisms between conformations and small molecules. “la Caixa” Foundation (project OSLC-2012-007), MINECO, (CTQ2014- 58812-C2-2-R) and Junta de Castilla y León, (BU042U16), FEDER Funds Spain application/pdf eng Elsevier Biochimica et biophysica acta (BBA) - general subjects. 2018, V. 1862, n. 3, p. 522-531 https://doi.org/10.1016/j.bbagen.2017.10.020 info:eu-repo/grantAgreement/“la Caixa” Foundation/OSLC-2012-007 info:eu-repo/grantAgreement/MINECO/CTQ2014-58812-C2-2-R info:eu-repo/grantAgreement/JCyL/BU042U16 Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess Tel22 conformations TMPyP4 Fast reactions Molecular dynamics Chemistry, Physical and theoretical Química física Kinetic evidence for interaction of TMPyP4 with two different G-quadruplex conformations of human telomeric DNA info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion CC-LICENSE license_rdf license_rdf application/rdf+xml; charset=utf-8 805 https://riubu.ubu.es/bitstream/10259/4746/8/license_rdf 4460e5956bc1d1639be9ae6146a50347 MD5 8 THUMBNAIL Pérez-BBAGS_2018.pdf.jpg Pérez-BBAGS_2018.pdf.jpg IM Thumbnail image/jpeg 4336 https://riubu.ubu.es/bitstream/10259/4746/7/P%c3%a9rez-BBAGS_2018.pdf.jpg ee77a2e5c03737dc5ea692384188a8f2 MD5 7 ORIGINAL Pérez-BBAGS_2018.pdf Pérez-BBAGS_2018.pdf application/pdf 1887931 https://riubu.ubu.es/bitstream/10259/4746/1/P%c3%a9rez-BBAGS_2018.pdf 658b8f0e26f04d639bafa8115581de23 MD5 1 LICENSE license.txt license.txt text/plain; charset=utf-8 999 https://riubu.ubu.es/bitstream/10259/4746/5/license.txt b295bcbce42e2caabeb0c623d3860c06 MD5 5 TEXT Pérez-BBAGS_2018.pdf.txt Pérez-BBAGS_2018.pdf.txt Extracted text text/plain 48068 https://riubu.ubu.es/bitstream/10259/4746/6/P%c3%a9rez-BBAGS_2018.pdf.txt b3e7de3f9a163511099506688a849560 MD5 6 10259/4746 oai:riubu.ubu.es:10259/4746 2022-04-29 14:02:48.948 Repositorio Institucional de la Universidad de Burgos bubrep@ubu.es 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