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Angew Chem Int Ed Engl. 2016 Mar 18;55(13):4256-9. doi: 10.1002/anie.201511999. Epub 2016 Mar 1.

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.

Author information

1
Dipartimento di Chimica 'Ugo Schiff', Università degli Studi di Firenze, Via della Lastruccia 3, 50019, Sesto Fiorentino, FI, Italy.
2
Dipartimento di Chimica 'Ugo Schiff', Università degli Studi di Firenze, Via della Lastruccia 3, 50019, Sesto Fiorentino, FI, Italy. marta.ferraroni@unifi.it.
3
Dipartimento di Neuroscienze, Psicologia, Area del Farmaco, Salute del Bambino (NEUROFARBA), Università degli Studi di Firenze, via Ugo Schiff 6, 50019, Sesto Fiorentino, FI, Italy.
4
UMR 6302 CNRS Université de Bourgogne, Dijon, France.
5
Dipartimento di Neuroscienze, Psicologia, Area del Farmaco, Salute del Bambino (NEUROFARBA), Università degli Studi di Firenze, via Ugo Schiff 6, 50019, Sesto Fiorentino, FI, Italy. paola.gratteri@unifi.it.
6
School of Chemistry, Cardiff University, Cardiff, CF103AT, 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:

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

PMID:
26929051
DOI:
10.1002/anie.201511999
[Indexed for MEDLINE]

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