Conformational Change in a Four-Tetrad DNA G-Quadruplex upon Intercalation of a Small-Molecule Ligand PyDH2.

ABSTRACT: G-quadruplexes (G4s) are non-canonical DNA structures implicated in a number of biological processes. Small-molecule ligands can alter stability and folding of G4s, which can potentially be exploited for therapeutic purposes. In this work, we investigate the interaction of telomeric DNA fragment from Tetrahymena thermophila (TET25, 5'-G(TTGGGG)_4-3') with a G4 ligand PyDH2 belonging to the bisquinolinium family. When alone, TET25 adopts a mixture of three conformations, with the most abundant being a four-tetrad hybrid G4. In the presence of PyDH2, surprisingly, TET25 folds into an antiparallel chair G4, with PyDH2 intercalated between G-tetrads 2 and 3, according to our crystal structure. The structure represents the second example, and the first crystallographic evidence, of li

SUBMITTER: Martin KN 

PROVIDER: S-EPMC12240457 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature