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
International audience; 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 invitro 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)]…
[Au(9-methylcaffein-8-ylidene) 2 ] + /DNA Tel23 System: Solution, Computational, and Biological Studies
International audience; Physicochemical methods have been used to investigate interactions occurring in solution between the dicarbene gold(I) complex [Au(9‐methylcaffein‐8‐ylidene)2]BF4 (AuNHC) and a human telomeric DNA sequence, namely Tel23. Circular dichroism measurements allow identification of the conformational changes experienced by Tel23 upon interaction with AuNHC, and the respective binding stoichiometries and constants were determined. Computational studies provide a good link between previous crystallographic results of the same system and the present solution data, offering an exhaustive description of the inherent noncovalent metallodrug–DNA interactions. Remarkably, we found…