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Title: | The effect of l-thymidine, acyclic thymine and 8-bromoguanine on the stability of model G-quadruplex structures |
Author: | Aviñó Andrés, Anna Mazzini, Stefania Fàbrega i Claveria, Ma. Carme Peñalver, Pablo Gargallo Gómez, Raimundo Morales, J.C. Eritja i Casadellà, Ramon |
Keywords: | Biologia molecular Bioquímica Oligonucleòtids G-estructures Molecular biology Biochemistry Oligonucleotides G-structures |
Issue Date: | 2-Oct-2016 |
Publisher: | Elsevier B.V. |
Abstract: | 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. |
Note: | Versió postprint del document publicat a: https://doi.org/10.1016/j.bbagen.2016.09.030 |
It is part of: | Biochimica et Biophysica Acta-General Subjects, 2017, vol. 1861, num. 5, Part B, p. 1205-1212 |
URI: | http://hdl.handle.net/2445/107055 |
Related resource: | https://doi.org/10.1016/j.bbagen.2016.09.030 |
ISSN: | 0304-4165 |
Appears in Collections: | Articles publicats en revistes (Enginyeria Química i Química Analítica) |
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