Enhancing G-Quadruplex Binding: Rational Design and Biophysical Evaluation of Dimeric Ligands.

ABSTRACT: G-quadruplexes (G4s) are non-canonical nucleic acid structures formed by guanine-rich sequences. Within the human genome, beyond telomeres, G4 motifs have also been found in promoters, implying a potential role in gene regulation that could be achieved through interactions with small-molecule ligands. In this field, anthraquinone represented a privileged scaffold for the design of G4-targeting molecules. Additionally, emerging evidence proved that compounds bearing two aromatic cores can offer enhanced affinity and selectivity toward G4s due to cooperative binding in a tweezer-like fashion. This study reports the rational design and synthesis of anthraquinone-based building blocks conceived to generate a dimeric ligand connected through a flexible polyethylene glycol (PEG) linker to potent

SUBMITTER: Giannangeli M 

PROVIDER: S-EPMC12731523 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature