Linker Design Principles for the Precision Targeting of Oncogenic G-Quadruplex DNA with G4-Ligand-Conjugated Oligonucleotides.

ABSTRACT: G-quadruplex (G4) DNA structures are noncanonical secondary structures found in key regulatory regions of the genome, including oncogenic promoters and telomeres. Small molecules, known as G4 ligands, capable of stabilizing G4s hold promise as chemical probes and therapeutic agents. Nevertheless, achieving precise specificity for individual G4 structures within the human genome remains a significant challenge. To address this, we expand upon G4-ligand-conjugated oligonucleotides (GL-Os), a modular platform combining the stabilizing properties of G4-ligands with the sequence specificity of guide DNA oligonucleotides. Central to this strategy is the linker that bridges the G4 ligand and the guide oligonucleotide. In this study, we develop multiple conjugation strategies for the GL-Os that en

SUBMITTER: Abrahamsson A 

PROVIDER: S-EPMC12006964 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature