Affinity variation in the interactions of tryptophan- β-cyclodextrin-platinum complex with G-quadruplex and duplex DNAs

Abstract

DNA forms non-canonical Guanine-rich-quadruplex structures that play crucial roles such as maintenance of the telomere, transcription, and replication. Selective binding of small molecular ligands to G-quadruplexes and stabilization of them gain importance in the control of cell proliferation and development of therapeutics. In this paper, we report the synthesis of a tryptophan-β-cyclodextrin complex and its platinum complex. The binding interaction of the synthesized Trp-β-CD-Pt compound with various DNAs, including a duplex DNA and three quadruplexes, are investigated. The binding of the compound to quadruplexes shows a general increase in the binding strength compared to the strength of binding with the duplex, CT-DNA. The compound reveals the strongest binding with kit22. An enhancement of fluorescence is generally observed when the ligand binds to all the DNAs, except myc22. The structure of the host: guest complex with Berberine, a model G-quadruplex binding ligand, is investigated using 2 D ROESY spectroscopy. The host: guest binding is strong and the DNA interaction does not extract much of the Berberine molecule from the complex. The differential bindings of the ligand in free- and Berberine-loaded forms with different G-quadruplexes are discussed in detail based on binding strengths and the modulation of fluorescence.

Communicated by Ramaswamy H. Sarma

Keywords:

• β-cyclodextrin conjugate
• Tryptophan
• Platinum complex
• Berberine
• G-quadruplex

Disclosure statement

No potential conflict of interest was reported by the authors.

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.