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[Au(9‐methylcaffein‐8‐ylidene) 2 ] + /DNA Tel23 System: Solution, Computational, and Biological Studies
Author(s) -
Papi Francesco,
Bazzicalupi Carla,
Ferraroni Marta,
Massai Lara,
Bertrand Benoît,
Gratteri Paola,
Colangelo Donato,
Messori Luigi
Publication year - 2017
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201702854
Subject(s) - chemistry , adduct , dna , circular dichroism , stoichiometry , stereochemistry , combinatorial chemistry , computational chemistry , crystallography , biochemistry , organic chemistry
Abstract Physicochemical methods have been used to investigate interactions occurring in solution between the dicarbene gold(I) complex [Au(9‐methylcaffein‐8‐ylidene) 2 ]BF 4 (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.