Differential interaction of Fluorescein-β-cyclodextrin conjugate to quadruplex kit22 DNA: Inclusion of Berberine and modulation of binding

Clinical applicability of G-quadruplexes as anticancer drugs is an area of current interest. Identification of supramolecular systems for selective targeting G-quartets is particularly intriguing. In this work, the DNA binder Berberine is encapsulated inside the molecular cavity of the synthesised host structure, Fluoresecein-beta-cyclodextrin conjugate. The host: guest complex is characterized and the mode of binding is optimized using two dimensional rotating-frame Overhauser effect spectroscopy. The conjugate is examined for its binding to quadruplex DNAs viz., kit22, myc22, telo24 and the duplex calf-thymus DNA before and after Berberine encapsulation. UV-vis and fluorescence spectroscopic methods were employed to determine the strength of binding of the complex with the DNAs. The binding strength and the stoichiometry of the host: guest complex are 1.9 x 10(6) mol(-1) dm(3) and 1:1, respectively. A quenching of fluorescence of the quadruplex kit22 and duplex ctDNA is observed on binding to the Fluorescein-beta-cyclodextrin conjugate. The quadruplexes of myc22 and telo24 display an enhanced fluorescence on binding to the modified cyclodextrin. The Stern-Volmer quenching constants are 1.4 x 10(6) mol(-1) dm(3) and 3.8 x 10(5) mol(-1) dm(3) for binding to kit22 and ctDNA respectively. kit22 shows a different emission profile on interacting with the Berberine encapsulated conjugate, whereas all the other quadruplexes and duplex exhibit similar emission profiles. The results indicate a variation in the binding mode and strength of the ligand-quadruplexes and depend on the conformation of the quadruplexes.

Automated summary

This study investigated the DNA binding behavior of Berberine encapsulated in the Fluorescein-beta-cyclodextrin conjugate. The results showed that the binding mode and strength varied depending on the conformation of the G-quadruplexes.