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Tailored Transition‐Metal Coordination Environments in Imidazole‐Modified DNA G‐Quadruplexes
Author(s) -
Punt Philip M.,
Clever Guido H.
Publication year - 2019
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201903445
Subject(s) - imidazole , chemistry , ligand (biochemistry) , affinities , binding affinities , g quadruplex , deoxyribozyme , transition metal , crystallography , oligonucleotide , metal , coordination complex , dna , stereochemistry , organic chemistry , biochemistry , receptor , catalysis
Two types of imidazole ligands were introduced both at the end of tetramolecular and into the loop region of unimolecular DNA G‐quadruplexes. The modified oligonucleotides were shown to complex a range of different transition‐metal cations including Ni II , Cu II , Zn II and Co II , as indicated by UV/Vis absorption spectroscopy and ion mobility mass spectrometry. Molecular dynamics simulations were performed to obtain structural insight into the investigated systems. Variation of ligand number and position in the loop region of unimolecular sequences derived from the human telomer region (htel) allows for a controlled design of distinct coordination environments with fine‐tuned metal affinities. It is shown that Cu II , which is typically square‐planar coordinated, has a higher affinity for systems offering four ligands, whereas Ni II prefers G‐quadruplexes with six ligands. Likewise, the positioning of ligands in a square‐planar versus tetrahedral fashion affects binding affinities of Cu II and Zn II cations, respectively. Gaining control over ligand arrangement patterns will spur the rational development of transition‐metal‐modified DNAzymes. Furthermore, this method is suited to combine different types of ligands, for example, those typically found in metalloenzymes, inside a single DNA architecture.