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Determinants for Tight and Selective Binding of a Medicinal Dicarbene Gold(I) Complex to a Telomeric DNA G‐Quadruplex: a Joint ESI MS and XRD Investigation |
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| Authors: | Prof. Carla Bazzicalupi Dr. Marta Ferraroni Francesco Papi Dr. Lara Massai Dr. Benoît Bertrand Prof. Luigi Messori Prof. Paola Gratteri Prof. Angela Casini |
| Affiliation: | 1. Dipartimento di Chimica ‘Ugo Schiff', Università degli Studi di Firenze, Sesto Fiorentino, FI, Italy;2. Dipartimento di Neuroscienze, Psicologia, Area del Farmaco, Salute del Bambino (NEUROFARBA), Università degli Studi di Firenze, Sesto Fiorentino, FI, Italy;3. UMR 6302 CNRS Université de Bourgogne, Dijon, France;4. School of Chemistry, Cardiff University, Cardiff, UK |
| Abstract: | The dicarbene gold(I) complex [Au(9‐methylcaffein‐8‐ylidene)2]BF4 is an exceptional organometallic compound of profound interest as a prospective anticancer agent. This gold(I) complex was previously reported to be highly cytotoxic toward various cancer cell lines in vitro and behaves as a selective G‐quadruplex stabilizer. Interactions of the gold complex with various telomeric DNA models have been analyzed by a combined ESI MS and X‐ray diffraction (XRD) approach. ESI MS measurements confirmed formation of stable adducts between the intact gold(I) complex and Tel 23 DNA sequence. The crystal structure of the adduct formed between [Au(9‐methylcaffein‐8‐ylidene)2]+ and Tel 23 DNA G‐quadruplex was solved. Tel 23 maintains a characteristic propeller conformation while binding three gold(I) dicarbene moieties at two distinct sites. Stacking interactions appear to drive noncovalent binding of the gold(I) complex. The structural basis for tight gold(I) complex/G‐quadruplex recognition and its selectivity are described. |
| Keywords: | cancer ESI mass spectrometry gold G-quadruplexes X-ray diffraction |