Interaction of 9-Methoxyluminarine with Different G-Quadruplex Topologies: Fluorescence and Circular Dichroism Studies.

Joanna Nowak-Karnowska,Joanna Kosman,Anna Dembska,Grażyna Neunert,Agata Głuszyńska

doi:10.3390/ijms221910399

Abstract

The interactions of G–quadruplexes of different topologies with highly fluorescent 9-methoxyluminarine ligand 9-MeLM were investigated by fluorescence and circular dichroism spectroscopy. The results showed that 9-methoxyluminarine was able to interact and did not destabilize any investigated molecular targets. The studied compound was selectively quenched by parallel c-MYC G-quadruplex DNA, whereas hybrid and antiparallel G4 topology caused only a negligible decrease in the fluorescence of the ligand. A high decrease of fluorescence of the ligand after binding with c-MYC G-quadruplex suggests that this molecule can be used as a selective probe for parallel G-quadruplexes.

Highlights

Guanine-rich sequences able to fold into non-canonical four-stranded nucleic acid structures under physiological conditions, called G-quadruplexes (G4s), have received particular attention in recent years due to their interesting structural features and biological functions [1]
9-methoxyluminarine ligand (9-MeLM) in Tris-HCl buffer was excited at λex = 390 nm and the recorded spectrum exhibited an unstructured emission band with a maximum of 495 nm
Fluorescence titration experiments were performed at a fixed concentration of 9-MeLM, by adding increasing amounts of each G-quadruplex or double-stranded DNA (ESI Figure S1)

Summary

Introduction

Guanine-rich sequences able to fold into non-canonical four-stranded nucleic acid structures under physiological conditions, called G-quadruplexes (G4s), have received particular attention in recent years due to their interesting structural features and biological functions [1] These sequences are present in the human genome, in telomeric DNA repeats [2] and key regulatory regions of the cell, such as promoters of proto-oncogenes (c-MYC [3,4,5,6], BCL-2 [7,8] and c-KIT [9,10,11]), and in untranslated regions of mRNA [12,13] and telomeric repeat-containing RNA (TERRA) [14,15]. Flat-shaped compounds (such as NMM IX or crystal violet) that were originally developed in different fields are often re- recognized as G-quadruplex binding ligands due to their planar geometry and availability [50]

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Results

Discussion

Conclusion