Title:
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The effect of l-thymidine, acyclic thymine and 8-bromoguanine on the stability of model G-quadruplex structures
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Author:
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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
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Other authors:
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Universitat de Barcelona |
Abstract:
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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. |
Subject(s):
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-Biologia molecular -Bioquímica -Oligonucleòtids -G-estructures -Molecular biology -Biochemistry -Oligonucleotides -G-structures |
Rights:
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cc-by-nc-nd (c) Elsevier B.V., 2016
info:eu-repo/semantics/embargoedAccess
http://creativecommons.org/licenses/by-nc-nd/3.0/es |
Document type:
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Article Article - Accepted version |
Published by:
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Elsevier B.V.
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