FeII 4L4 tetrahedron binds and aggregates DNA G-quadruplexes.

Jinbo Zhu,Jin Wang,Zhiqiang Yan,Filip Bošković,Ulrich F Keyser,Jonathan R Nitschke,Marion Kieffer,Cally J E Haynes,Jake L Greenfield

doi:10.1039/d1sc04430c

Abstract

Since the discovery of the G-quadruplex (G4) structure in telomeres in 1980s, studies have established the role it plays in various biological processes. Here we report binding between DNA G4 and a self-assembled tetrahedral metal-organic cage 1 and consequent formation of aggregates, whereby the cage protects the DNA G4 from cleavage by S1 nuclease. We monitor DNA–cage interaction using fluorescence spectroscopy, firstly by quenching of a fluorescent label appended to the 5′ end of G4. Secondly, we detect the decrease in fluorescence of the G4-selective dyes thioflavin-T and Zn-PPIX bound to various DNA G4 sequences following the addition of cage 1. Our results demonstrate that 1 interacts with a wide range of G4s. Moreover, gel electrophoresis, circular dichroism and dynamic light scattering measurements establish the binding of 1 to G4 and indicate the formation of aggregate structures. Finally, we find that DNA G4 contained in an aggregate of cage 1 is protected from cleavage by S1 nuclease.

Highlights

The DNA G-quadruplex (G4) is a four-stranded helical structure formed by the stacking of two or more planar G-tetrads on top of each other, with every G-tetrad containing four guanine bases associated through Hoogsteen hydrogen bonds.[1]
We detect the decrease in fluorescence of the G4-selective dyes thioflavin-T and Zn-PPIX bound to various DNA G4 sequences following the addition of cage 1
We find that DNA G4 contained in an aggregate of cage 1 is protected from cleavage by S1 nuclease

Summary

Introduction

The DNA G-quadruplex (G4) is a four-stranded helical structure formed by the stacking of two or more planar G-tetrads on top of each other, with every G-tetrad containing four guanine bases associated through Hoogsteen hydrogen bonds.[1]. We reported that the water-soluble FeI4IL4tetrahedral cage 1 (Fig. 1b)[39] can bind to unpaired nucleotides in DNA and thereby quench a proximate uorescent label.[33,40] Interact with Tel[22], as evidenced by the quenching of the uorescent dyes label or bound on the G4 strand.

Results

Conclusion