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 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.
Departamento de Síntesis, Estructura y Propiedades de Compuestos Orgánicos (SEPCO), Instituto de Química Orgánica general CSIC, c/Juan de la Cierva 3, 28006, Madrid, Spain.
Pablo
P
Peñalver
Filipa
F
Marcelo
Jesús
J
Jiménez-Barbero
Cristina
C
Vicent
D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry; D001483:Base Sequence; D002241:Carbohydrates / Q000737:chemistry*; D005690:Galactose / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D006001:Glycoconjugates / Q000737:chemistry*; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D000577:Amides; D002241:Carbohydrates; D006001:Glycoconjugates; D007211:Indoles; D009838:Oligodeoxyribonucleotides; D011758:Pyrroles; C558629:beta-Gal-Py-gamma-Py-Ind; D005690:Galactose