3 publications
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Highly Efficient Cyclic Dinucleotide Based Artificial Metalloribozymes for Enantioselective Friedel–Crafts Reactions in Water
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Angew. Chem. Int. Ed. 2020, 59, 3444-3449, 10.1002/anie.201912962
The diverse secondary structures of nucleic acids are emerging as attractive chiral scaffolds to construct artificial metalloenzymes (ArMs) for enantioselective catalysis. DNA‐based ArMs containing duplex and G‐quadruplex scaffolds have been widely investigated, yet RNA‐based ArMs are scarce. Here we report that a cyclic dinucleotide of c‐di‐AMP and Cu2+ ions assemble into an artificial metalloribozyme (c‐di‐AMP⋅Cu2+) that enables catalysis of enantioselective Friedel–Crafts reactions in aqueous media with high reactivity and excellent enantioselectivity of up to 97 % ee. The assembly of c‐di‐AMP⋅Cu2+ gives rise to a 20‐fold rate acceleration compared to Cu2+ ions. Based on various biophysical techniques and density function theory (DFT) calculations, a fine coordination structure of c‐di‐AMP⋅Cu2+ metalloribozyme is suggested in which two c‐di‐AMP form a dimer scaffold and the Cu2+ ion is located in the center of an adenine‐adenine plane through binding to two N7 nitrogen atoms and one phosphate oxygen atom.
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Novel Artificial Metalloenzymes by In Vivo Incorporation of Metal-Binding Unnatural Amino Acids
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Chem. Sci. 2015, 6, 770-776, 10.1039/c4sc01525h
Artificial metalloenzymes have emerged as an attractive new approach to enantioselective catalysis. Herein, we introduce a novel strategy for preparation of artificial metalloenzymes utilizing amber stop codon suppression methodology for the in vivo incorporation of metal-binding unnatural amino acids. The resulting artificial metalloenzymes were applied in catalytic asymmetric Friedel–Crafts alkylation reactions and up to 83% ee for the product was achieved.
Metal: CuLigand type: BipyridineHost protein: Lactoccal multidrug resistant regulator (LmrR)Anchoring strategy: ---Optimization: GeneticNotes: ---
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Supramolecular Assembly of Artificial Metalloenzymes Based on the Dimeric Protein LmrR as Promiscuous Scaffold
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J. Am. Chem. Soc. 2015, 137, 9796-9799, 10.1021/jacs.5b05790
Supramolecular anchoring of transition metal complexes to a protein scaffold is an attractive approach to the construction of artificial metalloenzymes since this is conveniently achieved by self-assembly. Here, we report a novel design for supramolecular artificial metalloenzymes that exploits the promiscuity of the central hydrophobic cavity of the transcription factor Lactococcal multidrug resistance Regulator (LmrR) as a generic binding site for planar coordination complexes that do not provide specific protein binding interactions. The success of this approach is manifested in the excellent enantioselectivities that are achieved in the Cu(II) catalyzed enantioselective Friedel–Crafts alkylation of indoles.
Metal: CuLigand type: PhenanthrolineHost protein: Lactoccal multidrug resistant regulator (LmrR)Anchoring strategy: SupramolecularOptimization: GeneticNotes: ---