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

Carla Bazzicalupi, Marta Ferraroni, Francesco Papi, Lara Massai, Benoît Bertrand, Luigi Messori, Paola Gratteri, Angela Casini

Research output: Contribution to journalArticlepeer-review

96 Scopus citations

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. Ready for takeoff: A crystal structure analysis of the adduct formed between [Au(9-methylcaffein-8-ylidene)2]+ and Tel 23 DNA G-quadruplex is presented. In the adduct, Tel 23 maintains a characteristic propeller conformation, while binding three gold(I) dicarbene moieties at two distinct sites.

Original languageEnglish
Pages (from-to)4256-4259
Number of pages4
JournalAngewandte Chemie International Edition in English
Volume55
Issue number13
DOIs
StatePublished - 18 Mar 2016
Externally publishedYes

Keywords

  • ESI mass spectrometry
  • G-quadruplexes
  • X-ray diffraction
  • cancer
  • gold

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