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Copper‐Induced Topology Switching and Thrombin Inhibition with Telomeric DNA G‐Quadruplexes
Author(s) -
Engelhard David M.,
Nowack Julia,
Clever Guido H.
Publication year - 2017
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201705724
Subject(s) - antiparallel (mathematics) , topology (electrical circuits) , chemistry , ligand (biochemistry) , g quadruplex , dna , intramolecular force , stereochemistry , oligonucleotide , tetrahymena , crystallography , receptor , biochemistry , physics , mathematics , combinatorics , quantum mechanics , magnetic field
The topological diversity of DNA G‐quadruplexes may play a crucial role in its biological function. Reversible control over a specific folding topology was achieved by the synthesis of a chiral, glycol‐based pyridine ligand and its fourfold incorporation into human telomeric DNA by solid‐phase synthesis. Square‐planar coordination to a Cu II ion led to the formation of a highly stabilizing intramolecular metal–base tetrad, substituting one G‐tetrad in the parent unimolecular G‐quadruplex. For the Tetrahymena telomeric repeat, Cu II ‐triggered switching from a hybrid‐dominated conformer mixture to an antiparallel topology was observed. Cu II ‐dependent control over a protein–G‐quadruplex interaction was shown for the thrombin–tba pair (tba=thrombin‐binding aptamer).