title: 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.
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.
authors.affiliation: Dipartimento di Chimica 'Ugo Schiff', Università degli Studi di Firenze, Via della Lastruccia 3, 50019, Sesto Fiorentino, FI, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Bazzicalupi
authors.affiliation: Dipartimento di Chimica 'Ugo Schiff', Università degli Studi di Firenze, Via della Lastruccia 3, 50019, Sesto Fiorentino, FI, Italy. marta.ferraroni@unifi.it.
authors.forename: Marta
authors.identifier: http://orcid.org/0000-0001-7258-738X
authors.initials: M
authors.lastname: Ferraroni
authors.affiliation: Dipartimento di Chimica 'Ugo Schiff', Università degli Studi di Firenze, Via della Lastruccia 3, 50019, Sesto Fiorentino, FI, Italy.|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.
authors.forename: Francesco
authors.initials: F
authors.lastname: Papi
authors.affiliation: Dipartimento di Chimica 'Ugo Schiff', Università degli Studi di Firenze, Via della Lastruccia 3, 50019, Sesto Fiorentino, FI, Italy.
authors.forename: Lara
authors.initials: L
authors.lastname: Massai
authors.affiliation: UMR 6302 CNRS Université de Bourgogne, Dijon, France.
authors.forename: Benoît
authors.initials: B
authors.lastname: Bertrand
authors.affiliation: Dipartimento di Chimica 'Ugo Schiff', Università degli Studi di Firenze, Via della Lastruccia 3, 50019, Sesto Fiorentino, FI, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Messori
authors.affiliation: 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.
authors.forename: Paola
authors.initials: P
authors.lastname: Gratteri
authors.affiliation: School of Chemistry, Cardiff University, Cardiff, CF103AT, UK.
authors.forename: Angela
authors.initials: A
authors.lastname: Casini
mesh_terms: D054856:G-Quadruplexes; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D016615:Telomere; D014961:X-Ray Diffraction / Q000379:methods*
keywords: ESI mass spectrometry; G-quadruplexes; X-ray diffraction; cancer; gold