3 research outputs found
Exploring the Dispersion and Electrostatic Components in Arene–Arene Interactions between Ligands and G4 DNA to Develop G4-Ligands
G-Quadruplex (G4)
DNA structures are important regulatory elements
in central biological processes. Small molecules that selectively
bind and stabilize G4 structures have therapeutic potential, and there
are currently >1000 known G4 ligands. Despite this, only two G4
ligands
ever made it to clinical trials. In this work, we synthesized several
heterocyclic G4 ligands and studied their interactions with G4s (e.g.,
G4s from the c-MYC, c-KIT, and BCL-2 promoters) using biochemical assays. We further studied
the effect of selected compounds on cell viability, the effect on
the number of G4s in cells, and their pharmacokinetic properties.
This identified potent G4 ligands with suitable properties and further
revealed that the dispersion component in arene–arene interactions
in combination with electron-deficient electrostatics is central for
the ligand to bind with the G4 efficiently. The presented design strategy
can be applied in the further development of G4-ligands with suitable
properties to explore G4s as therapeutic targets
Exploring the Dispersion and Electrostatic Components in Arene–Arene Interactions between Ligands and G4 DNA to Develop G4-Ligands
G-Quadruplex (G4)
DNA structures are important regulatory elements
in central biological processes. Small molecules that selectively
bind and stabilize G4 structures have therapeutic potential, and there
are currently >1000 known G4 ligands. Despite this, only two G4
ligands
ever made it to clinical trials. In this work, we synthesized several
heterocyclic G4 ligands and studied their interactions with G4s (e.g.,
G4s from the c-MYC, c-KIT, and BCL-2 promoters) using biochemical assays. We further studied
the effect of selected compounds on cell viability, the effect on
the number of G4s in cells, and their pharmacokinetic properties.
This identified potent G4 ligands with suitable properties and further
revealed that the dispersion component in arene–arene interactions
in combination with electron-deficient electrostatics is central for
the ligand to bind with the G4 efficiently. The presented design strategy
can be applied in the further development of G4-ligands with suitable
properties to explore G4s as therapeutic targets
Metody pro hodnocení přesnosti digitálních měřících systémů
Import 20/04/2006Prezenční výpůjčkaVŠB - Technická univerzita Ostrava. Fakulta elektrotechniky a informatiky