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

Abstract

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-β-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 × 10⁶ mol⁻¹ dm³ and 1:1, respectively. A quenching of fluorescence of the quadruplex kit22 and duplex ctDNA is observed on binding to the Fluorescein-β-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 × 10⁶ mol⁻¹ dm³ and 3.8 × 10⁵ mol⁻¹ dm³ 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.

Communicated by Ramaswamy H. Sarma

Keywords:

• Fluorescein-β-cyclodextrin conjugate
• Berberine
• G-quadruplex
• ctDNA
• host: guest complex

Disclosure statement

The authors declare no conflict of interest.

Additional information

Funding

The authors thank the Department of Atomic Energy (DAE)–Board of Research in Nuclear Sciences (BRNS), Government of India, for the project: 37(2)/14/17/2018-BRNS.