Revisiting recent unusual drug-DNA complex structures: Implications for cancer and neurological disease diagnostics and therapeutics

Abstract

DNA plays a crucial role in various biological processes such as protein production, replication, recombination etc. by adopting different conformations. Targeting these conformations by small molecules is not only important for disease therapy, but also improves our understanding of the mechanisms of disease development. In this review, we provide an overview of some of the most recent ligand-DNA complexes that have diagnostic and therapeutic applications in neurological diseases caused by abnormal repeat expansions and in cancer associated with mismatches. In addition, we have discussed important implications of ligands targeting higher-order structures, such as four-way junctions, G-quadruplexes and triplexes for drug discovery and DNA nanotechnology. We provide an overview of the results and perspectives of such structural studies on ligand-DNA interactions.

Keywords: Cancer; DNA mismatches; Ligand-DNA complexes; Neurological diseases; Nucleotide repeat expansion; Unusual nucleic acid structures.