6533b860fe1ef96bd12c3906
RESEARCH PRODUCT
[Au(9-methylcaffein-8-ylidene) 2 ] + /DNA Tel23 System: Solution, Computational, and Biological Studies
Marta FerraroniDonato ColangeloFrancesco PapiCarla BazzicalupiLara MassaiBenoît BertrandLuigi MessoriPaola Gratterisubject
0301 basic medicineCircular dichroismSequence (biology)G-quadruplextelomerasehuman telomeric dnaCatalysisantitumor agentsk+ solutionAdductg-quadruplex structures03 medical and health sciencesMolecular dynamicschemistry.chemical_compoundanticancer agentsDNA structuresgold carbenes[CHIM]Chemical SciencesBinding sitechemistry.chemical_classificationcomplexesdensityligand-bindingChemistryOrganic Chemistrystructural basisGeneral ChemistrysequenceCombinatorial chemistryG-quadruplexescircular dichroismcircular-dichroism030104 developmental biologyEnzymeDNAdescription
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 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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2017-10-04 |