1. Tailored Transition‐Metal Coordination Environments in Imidazole‐Modified DNA G‐Quadruplexes
- Author
-
Guido H. Clever and Philip M. Punt
- Subjects
Oligonucleotides ,Deoxyribozyme ,Molecular Dynamics Simulation ,010402 general chemistry ,G-quadruplex ,01 natural sciences ,Catalysis ,imidazole ,Coordination complex ,bioinorganic chemistry ,chemistry.chemical_compound ,Molecular dynamics ,Ion Mobility Spectrometry ,Transition Elements ,Transition Temperature ,Imidazole ,chemistry.chemical_classification ,Full Paper ,010405 organic chemistry ,Oligonucleotide ,Ligand ,Organic Chemistry ,Imidazoles ,DNA ,DNA, Catalytic ,General Chemistry ,Full Papers ,G-quadruplexes ,Affinities ,0104 chemical sciences ,Coordination Chemistry ,Crystallography ,chemistry - Abstract
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 NiII, CuII, ZnII and CoII, 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 CuII, which is typically square‐planar coordinated, has a higher affinity for systems offering four ligands, whereas NiII prefers G‐quadruplexes with six ligands. Likewise, the positioning of ligands in a square‐planar versus tetrahedral fashion affects binding affinities of CuII and ZnII 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., Unimolecular DNA G‐quadruplexes, modified with metallo‐enzyme‐inspired imidazole moieties, can be fine‐tuned to bind a variety of transition‐metal cations in their loop region.
- Published
- 2019