Supramolecular Recognition of a DNA Four-Way Junction by an M₂L₄ Metallo-Cage, Inspired by a Simulation-Guided Design Approach.

ABSTRACT: DNA four-way junctions (4WJs) play an important biological role in DNA repair and recombination, and viral regulation, and are attractive therapeutic targets. Compounds that recognise the junction structure are rare; in this work, we describe cationic metallo-supramolecular M₂L₄ cages as a new type of 4WJ binder with nanomolar affinities. A combination of molecular dynamics (MD) simulations and biophysical experiments show that the size and shape of a compound comprising square planar Pd or Pt and anthracene-based ligands is an excellent fit for the 4WJ cavity. Whilst the cage is also capable of binding to three-way junctions (3WJs) and Y-fork structures, we show that the 4WJ is the preferred DNA target, and that duplex B-DNA is not a competitor. Among 3WJs, T-shape b

SUBMITTER: Dettmer SJ 

PROVIDER: S-EPMC12184311 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature