Spectroscopic, Molecular Modeling, and NMR-Spectroscopic Investigation of the Binding Mode of the Natural Alkaloids Berberine and Sanguinarine to Human Telomeric G-Quadruplex DNA

• DOI: 10.1021/cb300096g
• Publication Date: 2012-04-09T20:09:02Z
• Authors: Irene Bessi; Carla Bazzicalupi; Christian Richter; Hendrik R. A. Jonker; Krishna Saxena; Claudia Sissi; Matteo Chioccioli; Sara Bianco; Anna Rita Bilia; Harald Schwalbe; Paola Gratteri
• Keywords: Benzophenanthridines; Models, Molecular; 0301 basic medicine; 0303 health sciences; Magnetic Resonance Spectroscopy; Berberine; Circular Dichroism; molecular modeling; spectroscopic investigation; DNA; G-quadruplex; natural alkaloids; DNA; Isoquinolines; 3. Good health; G-Quadruplexes; 03 medical and health sciences; Spectrometry, Fluorescence; Humans

G-quadruplex structures can be formed at the single-stranded overhang of telomeric DNA, and ligands able to stabilize this structure have recently been identified as potential anticancer drugs. Among the potential G-quadruplex binders, we have studied the binding ability of berberine and sanguinarine, two members of the alkaloid family, an important class of natural products long known for medicinal purpose. Our spectroscopic (CD, NMR, and fluorescence) studies and molecular modeling approaches revealed binding modes at ligand-complex stoichiometries >1:1 and ligand self-association induced by DNA for the interactions of the natural alkaloids berberine and sanguinarine with the human telomeric G-quadruplex DNA.