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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/107055
The effect of l-thymidine, acyclic thymine and 8-bromoguanine on the stability of model G-quadruplex structures
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Background Guanine-rich oligonucleotides are capable of forming tetrahelical structures known as G-quadruplexes with interesting biological properties. We have investigated the effects of site-specific substitution in the loops and in the tetrads model G-quadruplexes using thymine glycol nucleic acid (GNA) units, l-thymidine and 8-Br-2′-deoxyguanosine. Methods Modified oligonucleotides were chemically synthesized and spectroscopic techniques were used to determine the relative stability of the modified G-quadruplex. The double 8-BrdG-modified quadruplexes were further characterized by Nuclear Magnetic Resonance. Binding to thrombin of selected quadruplex was analyzed by gel electrophoresis retention assay. Results The most interesting results were found with a 8-bromoG substitution that had the larger stabilization of the quadruplex. NMR studies indicate a tight relationship between the loops and the tetrads to accommodate 8-bromoG modifications within the TBA. Conclusions The substitutions of loop positions with GNA T affect the TBA stability except for single modification in T7 position. Single l-thymidine substitutions produced destabilization of TBA. Larger changes on quadruplex stability are observed with the use of 8-bromoG finding a single substitution with the highest thermal stabilization found in thrombin binding aptamers modified at the guanine residues and having good affinity for thrombin. Double 8-BrdG modification in anti positions of different tetrads produce a conformational flip from syn to anti conformation of 8-Br-dG to favor loop-tetrad interaction and preserve the overall TBA stability.
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AVIÑÓ ANDRÉS, Anna, MAZZINI, Stefania, FÀBREGA I CLAVERIA, Ma. carme, PEÑALVER, Pablo, GARGALLO GÓMEZ, Raimundo, MORALES, J.c., ERITJA I CASADELLÀ, Ramon. The effect of l-thymidine, acyclic thymine and 8-bromoguanine on the stability of model G-quadruplex structures. _Biochimica et Biophysica Acta-General Subjects_. 2017. Vol. 1861, núm. 5, pàgs. Part B. [consulta: 24 de gener de 2026]. ISSN: 0304-4165. [Disponible a: https://hdl.handle.net/2445/107055]