Helical aromatic oligoamide foldamers as selective G-quadruplex ligands.

ABSTRACT: We investigated the G-quadruplex (G4) binding selectivity of short aromatic oligoamide helical foldamers comprising quinoline (Q) and pyridine (P) units. We found that the foldamers bind with 1:1 and 2:1 stoichiometries and prefer parallel G4 structures, especially when the external G-quartets are sterically accessible. A crystal structure of the tetramer QQPQ with the parallel G4 formed by dTGGGTTGGGTTGGGTTGGGT shows two quinoline subunits interacting with an external G-quartet through π-stacking, and solution nuclear magnetic resonance (NMR) confirms that the foldamer targets the 3' and 5' ends of this G4. Foldamers can also selectively target sequence variants of the telomeric sequences containing adenine-to-thymine mutation in the loops. The conformational selectivity of foldamers orig

SUBMITTER: Konig A 

PROVIDER: S-EPMC12754783 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature