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

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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.

3403 Macromolecular and Materials Chemistry, 34 Chemical Sciences, Genetics
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Chem Sci
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Royal Society of Chemistry (RSC)
Engineering and Physical Sciences Research Council (EP/M008258/1)
European Research Council (647144)