Title
[Au(9-methylcaffein-8-ylidene)2]+/DNA Tel23 System: Solution, Computational, and Biological Studies
Author
Francesco Papi, Carla Bazzicalupi, Marta Ferraroni, Lara Massai, Benoît Bertrand, Paola Gratteri, Donato Colangelo, Luigi Messori
Year
2017
Journal
Chemistry: A European Journal
Abstract
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 that a preformed AuNHC/Tel23 adduct is capable of producing strong and selective inhibition of the enzyme telomerase. The latter feature is mechanistically relevant and might account for the conspicuous in vitro anticancer properties of the investigated dicarbene gold(I) complex.
Instrument
J-810
Keywords
Circular dichroism, DNA structure, Ligand binding, Thermal stability, Biochemistry