Evaluation of the effect of polymorphism on G-quadruplex-ligand interaction by means of spectroscopic and chromatographic techniques

Guanine-rich sequences may fold into highly ordered structures known as G-quadruplexes. Apart from the monomeric G-quadruplex, these sequences may form multimeric structures that are not usually considered when studying interaction with ligands. This work studies the interaction of a ligand, crystal...

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Detalhes bibliográficos
Autores: Benito, S., Ferrer, A., Benavou, S., Aviñó, Anna, Eritja Casadellà, Ramón, Gargallo, Raimundo
Formato: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2018
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/161760
Acesso em linha:http://hdl.handle.net/10261/161760
Access Level:acceso abierto
Palavra-chave:G-quadruplex
Crystal violet
Binding equilibria
Polymorphism
Multivariate analysis
Descrição
Resumo:Guanine-rich sequences may fold into highly ordered structures known as G-quadruplexes. Apart from the monomeric G-quadruplex, these sequences may form multimeric structures that are not usually considered when studying interaction with ligands. This work studies the interaction of a ligand, crystal violet, with three guanine-rich DNA sequences with the capacity to form multimeric structures. These sequences correspond to short stretches found near the promoter regions of c-kit and SMARCA4 genes. Instrumental techniques (circular dichroism, molecular fluorescence, size-exclusion chromatography and electrospray ionization mass spectrometry) and multivariate data analysis were used for this purpose. The polymorphism of G-quadruplexes was characterized prior to the interaction studies. The ligand was shown to interact preferentially with the monomeric G-quadruplex; the binding stoichiometry was 1:1 and the binding constant was in the order of 105 M−1 for all three sequences. The results highlight the importance of DNA treatment prior to interaction studies.