Carbohydrate recognition at the minor-groove of the self-complementary duplex d(CGCGAATTCGCG)2 by a synthetic glyco-oligoamide

The structure of a neutral glyco-conjugate β-Gal-Py-γ-Py-Ind (1), designed as a probe for analyzing sugar-DNA interactions, when bound to a self-complementary oligonucleotide duplex d(CGCG AATT CGCG)(2) has been deduced by employing (1)H NMR techniques. Analysis of the formed 1:1 complex demonstrate...

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Detalhes bibliográficos
Autores: Peñalver, Pablo, Marcelo, Filipa, Jiménez-Barbero, Jesús, Vicent, Cristina
Formato: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2011
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/378096
Acesso em linha:http://hdl.handle.net/10261/378096
https://api.elsevier.com/content/abstract/scopus_id/79953689280
Access Level:acceso abierto
Palavra-chave:Carbohydrates
Conformation analysis
DNA recognition
Glycoconjugates
NMR spectroscopy
Descrição
Resumo:The structure of a neutral glyco-conjugate β-Gal-Py-γ-Py-Ind (1), designed as a probe for analyzing sugar-DNA interactions, when bound to a self-complementary oligonucleotide duplex d(CGCG AATT CGCG)(2) has been deduced by employing (1)H NMR techniques. Analysis of the formed 1:1 complex demonstrated that the glycol ligand is bound in a hairpin-like conformation in which both pyrrole amino acid moieties are stacked, whereas the indole and the sugar residues are spatially close. The binding site is defined by the minor groove formed by the -AATT- stretch. In particular, the -Py-γ-Py- region of the ligand is sited near the A5-A6 oligonucleotide residues, whereas the indole and the sugar rings are next to the T7-T8 base pairs. More relevant, the existence of a variety of intermolecular NOE correlations permitted the close proximity of the sugar to the minor groove to be assessed, thus showing that the binding of the glycoconjugate at the minor groove is the origin of the specificity of the glycoconjugate-DNA interaction. The experimental NMR data have been combined with restrained and unrestrained molecular dynamics calculations, to provide the 3D structure of the complex.