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Título

The effect of l-thymidine, acyclic thymine and 8-bromoguanine on the stability of model G-quadruplex structures

AutorAviñó, Anna; Mazzini, Stefania; Fàbrega, Carme; Peñalver, Pablo ; Gargallo, Raimundo; Morales, Juan Carlos; Eritja Casadellà, Ramón
Palabras clave8-bromo-2'-deoxyguanine
G-quadruplex
NMR
Thrombin binding aptamer
Thymine glycol nucleic acidl-thymidine
Fecha de publicación5-sep-2016
EditorElsevier
CitaciónBiochimica et Biophysica Acta - General Subjects
ResumenBackground: 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. General significance: Modified guanine-rich oligonucleotides are valuable tools for the search for G-quadruplex structures with higher thermal stability and may provide compounds with interesting protein-nucleic acid binding properties. This article is part of a Special Issue entitled "G-quadruplex" Guest Editor: Dr. Concetta Giancola and Dr. Daniela Montesarchio. © 2016.
Versión del editor10.1016/j.bbagen.2016.09.030
URIhttp://hdl.handle.net/10261/141161
DOI10.1016/j.bbagen.2016.09.030
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