Indoloquinoline Ligands Favor Intercalation at Quadruplex-Duplex Interfaces.

ABSTRACT: Quadruplex-duplex (Q-D) junctions are increasingly considered promising targets for medicinal and technological applications. Here, a Q-D hybrid with a hairpin-type snapback loop coaxially stacked onto the quadruplex 3'-outer tetrad was designed and employed as a target structure for the indoloquinoline ligand SYUIQ-5. NMR spectral analysis demonstrated high-affinity binding of the ligand at the quadruplex-duplex interface with association constants determined by isothermal titration calorimetry of about 10⁷  M^-1 and large exothermicities ΔH° of -14 kcal/mol in a 120 mM K⁺ buffer at 40 °C. Determination of the ligand-bound hybrid structure revealed intercalation of SYUIQ-5 between 3'-outer tetrad and the neighboring CG base pair, maximizing π-π stacking as

SUBMITTER: Vianney YM 

PROVIDER: S-EPMC9303235 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature