0000000001314853
AUTHOR
Katerina Duskova
showing 7 related works from this author
The Scope of Application of Macrocyclic Polyamines Beyond Metal Chelation
2019
Recent advances in the use of radiometals for both imaging and therapy has spurred on the development of an original chemistry that endows radionuclide-chelating molecular cages with ever sharper physicochemical properties. Macrocyclic polyamines (MPAs) such as cyclen and DOTA are among the most frequently encountered cages for the design of new radiotracers, owing to their versatile chemistry that makes them customizable molecular tools. The idea of using MPAs for alternative purposes has recently emerged, with an eye towards benefiting from their unique topology, versatility, symmetry and water-solubility. This review summarizes strategies that have been recently implemented in which MPAs…
Dual targeting of higher-order DNA structures by azacryptands induces DNA junction-mediated DNA damage in cancer cells
2021
Abstract DNA is intrinsically dynamic and folds transiently into alternative higher-order structures such as G-quadruplexes (G4s) and three-way DNA junctions (TWJs). G4s and TWJs can be stabilised by small molecules (ligands) that have high chemotherapeutic potential, either as standalone DNA damaging agents or combined in synthetic lethality strategies. While previous approaches have claimed to use ligands that specifically target either G4s or TWJs, we report here on a new approach in which ligands targeting both TWJs and G4s in vitro demonstrate cellular effects distinct from that of G4 ligands, and attributable to TWJ targeting. The DNA binding modes of these new, dual TWJ-/G4-ligands w…
Identification of Three-Way DNA Junction Ligands through Screening of Chemical Libraries and Validation by Complementary in Vitro Assays
2019
International audience; The human genome is replete with repetitive DNA sequences that can fold into thermodynamically stable secondary structures such as hairpins and quadruplexes. Cellular enzymes exist to cope with these structures whose stable accumulation would result in DNA damage through interference with DNA transactions such as transcription and replication. Therefore, the chemical stabilization of secondary DNA structures offers an attractive way to foster DNA transaction-associated damages to trigger cell death in proliferating cancer cells. While much emphasis has been recently given to DNA quadruplexes, we focused here on three-way DNA junctions (TWJ) and report on a strategy t…
The Scope of Application of Macrocyclic Polyamines Beyond Metal Chelation
2019
International audience; Recent advances in the use of radiometals for both imaging and therapy has spurred on the development of an original chemistry that endows radionuclide-chelating molecular cages with ever sharper physicochemical properties. Macrocyclic polyamines (MPAs) such as cyclen and DOTA are among the most frequently encountered cages for the design of new radiotracers, owing to their versatile chemistry that makes them customizable molecular tools. The idea of using MPAs for alternative purposes has recently emerged, with an eye towards benefiting from their unique topology, versatility, symmetry and water-solubility. This review summarizes strategies that have been recently i…
Front Cover: The Scope of Application of Macrocyclic Polyamines Beyond Metal Chelation (Eur. J. Org. Chem. 36/2019)
2019
International audience
DNA Junction Ligands Trigger DNA Damage and Are Synthetic Lethal with DNA Repair Inhibitors in Cancer Cells.
2019
International audience; Translocation of DNA and RNA polymerases along their duplex substrates results in DNA supercoiling. This torsional stress promotes the formation of plectonemic structures, including three-way DNA junction (TWJ), which can block DNA transactions and lead to DNA damage. While cells have evolved multiple mechanisms to prevent the accumulation of such structures, stabilizing TWJ through ad hoc ligands offer an opportunity to trigger DNA damage in cells with high level of transcription and replication, such as cancer cells. Here, we develop a series of azacryptand-based TWJ ligands, we thoroughly characterize their TWJ-interacting properties in vitro and demonstrate their…
CCDC 1952718: Experimental Crystal Structure Determination
2020
Related Article: Katerina Duskova, Pauline Lejault, Élie Benchimol, Régis Guillot, Sébastien Britton, Anton Granzhan, David Monchaud|2019|J.Am.Chem.Soc.|142|424|doi:10.1021/jacs.9b11150