Heteroleptic Coordination Environments in Metal-Mediated DNA G-Quadruplexes
The presence of metal centers with often highly conserved coordination environments is crucial for roughly half of all proteins, having structural, regulatory, or enzymatic function. To understand and mimic the function of metallo-enzymes, bioinorganic chemists pursue the challenge of synthesizing m...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-01-01
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| Series: | Frontiers in Chemistry |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fchem.2020.00026/full |
| _version_ | 1831654642090508288 |
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| author | Philip M. Punt Lukas M. Stratmann Sinem Sevim Lena Knauer Carsten Strohmann Guido H. Clever |
| author_facet | Philip M. Punt Lukas M. Stratmann Sinem Sevim Lena Knauer Carsten Strohmann Guido H. Clever |
| author_sort | Philip M. Punt |
| collection | DOAJ |
| description | The presence of metal centers with often highly conserved coordination environments is crucial for roughly half of all proteins, having structural, regulatory, or enzymatic function. To understand and mimic the function of metallo-enzymes, bioinorganic chemists pursue the challenge of synthesizing model compounds with well-defined, often heteroleptic metal sites. Recently, we reported the design of tailored homoleptic coordination environments for various transition metal cations based on unimolecular DNA G-quadruplex structures, templating the regioselective positioning of imidazole ligandosides LI. Here, we expand this modular system to more complex, heteroleptic coordination environments by combining LI with a new benzoate ligandoside LB within the same oligonucleotide. The modifications still allow the correct folding of parallel tetramolecular and antiparallel unimolecular G-quadruplexes. Interestingly, the incorporation of LB results in strong destabilization expressed in lower thermal denaturation temperatures Tm. While no transition metal cations could be bound by G-quadruplexes containing only LB, heteroleptic derivatives containing both LI and LB were found to complex CuII, NiII, and ZnII. Especially in case of CuII we found strong stabilizations of up to ΔTm = +34°C. The here shown system represents an important step toward the design of more complex coordination environments inside DNA scaffolds, promising to culminate in the preparation of functional metallo-DNAzymes. |
| first_indexed | 2024-12-19T16:31:54Z |
| format | Article |
| id | doaj.art-8c3f4ba0aac54a64a65f0ae8b9a31d29 |
| institution | Directory Open Access Journal |
| issn | 2296-2646 |
| language | English |
| last_indexed | 2024-12-19T16:31:54Z |
| publishDate | 2020-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Chemistry |
| spelling | doaj.art-8c3f4ba0aac54a64a65f0ae8b9a31d292022-12-21T20:14:10ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462020-01-01810.3389/fchem.2020.00026512196Heteroleptic Coordination Environments in Metal-Mediated DNA G-QuadruplexesPhilip M. PuntLukas M. StratmannSinem SevimLena KnauerCarsten StrohmannGuido H. CleverThe presence of metal centers with often highly conserved coordination environments is crucial for roughly half of all proteins, having structural, regulatory, or enzymatic function. To understand and mimic the function of metallo-enzymes, bioinorganic chemists pursue the challenge of synthesizing model compounds with well-defined, often heteroleptic metal sites. Recently, we reported the design of tailored homoleptic coordination environments for various transition metal cations based on unimolecular DNA G-quadruplex structures, templating the regioselective positioning of imidazole ligandosides LI. Here, we expand this modular system to more complex, heteroleptic coordination environments by combining LI with a new benzoate ligandoside LB within the same oligonucleotide. The modifications still allow the correct folding of parallel tetramolecular and antiparallel unimolecular G-quadruplexes. Interestingly, the incorporation of LB results in strong destabilization expressed in lower thermal denaturation temperatures Tm. While no transition metal cations could be bound by G-quadruplexes containing only LB, heteroleptic derivatives containing both LI and LB were found to complex CuII, NiII, and ZnII. Especially in case of CuII we found strong stabilizations of up to ΔTm = +34°C. The here shown system represents an important step toward the design of more complex coordination environments inside DNA scaffolds, promising to culminate in the preparation of functional metallo-DNAzymes.https://www.frontiersin.org/article/10.3389/fchem.2020.00026/fullbioinorganic chemistrycoordination chemistryDNAG-quadruplexDNAzymes |
| spellingShingle | Philip M. Punt Lukas M. Stratmann Sinem Sevim Lena Knauer Carsten Strohmann Guido H. Clever Heteroleptic Coordination Environments in Metal-Mediated DNA G-Quadruplexes Frontiers in Chemistry bioinorganic chemistry coordination chemistry DNA G-quadruplex DNAzymes |
| title | Heteroleptic Coordination Environments in Metal-Mediated DNA G-Quadruplexes |
| title_full | Heteroleptic Coordination Environments in Metal-Mediated DNA G-Quadruplexes |
| title_fullStr | Heteroleptic Coordination Environments in Metal-Mediated DNA G-Quadruplexes |
| title_full_unstemmed | Heteroleptic Coordination Environments in Metal-Mediated DNA G-Quadruplexes |
| title_short | Heteroleptic Coordination Environments in Metal-Mediated DNA G-Quadruplexes |
| title_sort | heteroleptic coordination environments in metal mediated dna g quadruplexes |
| topic | bioinorganic chemistry coordination chemistry DNA G-quadruplex DNAzymes |
| url | https://www.frontiersin.org/article/10.3389/fchem.2020.00026/full |
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