Authors: Stratmann, Lukas M.
Kutin, Yury
Kasanmascheff, Müge
Clever, Guido H.
Title: Precise distance measurements in DNA G-quadruplex dimers and sandwich complexes by pulsed dipolar EPR spectroscopy
Language (ISO): en
Abstract: DNA G-quadruplexes show a pronounced tendency to form higher-order structures, such as π-stacked dimers and aggregates with aromatic binding partners. Reliable methods for determining the structure of these non-covalent adducts are scarce. Here, we use artificial square-planar Cu(pyridine)4 complexes, covalently incorporated into tetramolecular G-quadruplexes, as rigid spin labels for detecting dimeric structures and measuring intermolecular Cu2+–Cu2+ distances via pulsed dipolar EPR spectroscopy. A series of G-quadruplex dimers of different spatial dimensions, formed in tail-to-tail or head-to-head stacking mode, were unambiguously distinguished. Measured distances are in full agreement with results of molecular dynamics simulations. Furthermore, intercalation of two well-known G-quadruplex binders, PIPER and telomestatin, into G-quadruplex dimers resulting in sandwich complexes was investigated, and previously unknown binding modes were discovered. Additionally, we present evidence that free G-tetrads also intercalate into dimers. Our transition metal labeling approach, combined with pulsed EPR spectroscopy, opens new possibilities for examining structures of non-covalent DNA aggregates.
Subject Headings: DNA
Metal base-pairing
EPR spectroscopy
Issue Date: 2020-10-16
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Appears in Collections:Lehrstühle für Anorganische Chemie

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