The crystal structure of human telomeric DNA complexed with berberine: an interesting case of stacked ligand to G-tetrad ratio higher than 1:1 |
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| Authors: | Carla Bazzicalupi Marta Ferraroni Anna Rita Bilia Francesca Scheggi Paola Gratteri |
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| Affiliation: | 1Department of Chemistry “Ugo Schiff”, University of Firenze, Via della Lastruccia 3-13, 2Department of Pharmaceutical Sciences and 3Laboratory of Molecular Modeling Cheminformatics & QSAR, Department of Pharmaceutical Sciences, University of Firenze, Via Ugo Schiff 6, I-50019 Sesto Fiorentino, Firenze, Italy |
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| Abstract: | The first crystal structure of human telomeric DNA in complex with the natural alkaloid berberine, produced by different plant families and used in folk medicine for millennia, was solved by X-ray diffraction method. The G-quadruplex unit features all-parallel strands. The overall folding assumed by DNA is the same found in previously reported crystal structures. Similarly to previously reported structures the ligand molecules were found to be stacked onto the external 5′ and 3′-end G-tetrads. However, the present crystal structure highlighted for the first time, the presence of two berberine molecules in the two binding sites, directly interacting with each tetrad. As a consequence, our structural data point out a 2:1 ligand to G-tetrad molar ratio, which has never been reported before in a telomeric intramolecular quadruplex structure. |
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