Molecularly Imprinted Polymers for Highly Specific Bioorthogonal Catalysis Inside Cells

Transition metal catalysts (TMCs) mediated bioorthogonal catalysis expand the chemical possibilities within cells. Developing synthetic TMCs tools that emulate the efficiency and specificity of natural metalloenzymes is a rewarding yet challenging endeavor. Here, we highlight the potential of molecu...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2024-12, Vol.63 (49), p.e202409849-n/a
Main Authors: Gao, Zhiguo, Shao, Quanlin, Xing, Jiaqi, Liang, Yi, Meng, Fanzhen, Chen, Jian, He, Wei, Li, Yaojia, Sun, Baiwang
Format: Article
Language:English
Subjects:
Artificial metalloenzymes
Bioorthogonal catalysis
Catalysis
Chemical reactions
Copper
Copper - chemistry
Copper - metabolism
Ductile-brittle transition
Gene switches
Glutathione
Humans
Imprinted polymers
Molecular Structure
Molecularly imprinted polymers
Molecularly Imprinted Polymers - chemistry
Polymers
Substrates
Thyroid
Thyroid gland
Transition metals
Triiodothyronine
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Summary:Transition metal catalysts (TMCs) mediated bioorthogonal catalysis expand the chemical possibilities within cells. Developing synthetic TMCs tools that emulate the efficiency and specificity of natural metalloenzymes is a rewarding yet challenging endeavor. Here, we highlight the potential of molecularly imprinted enzyme mimics (MIEs) containing a Cu center and specific substrate binding domain, for conducing dimethylpropargyloxycarbonyl (DmProc) cleavage reactions within cells. Our studies reveal that the Cu‐MIEs act as highly specific guides, precisely catalyzing target substrates, even in glutathione (GSH)‐rich cellular environments. By adapting templates similar to the target substrates, we evolved Cu‐MIEs activity to a high level and provided a method to broaden its scope to other unique substrates. This system was applied to a thyroid hormone (T3)‐responsive gene switch model, inducing firefly luciferase expression by T3 in cells. This approach verifies that MIEs effectively rescue DmProc‐bearing T3 prodrugs and seamlessly integrating themself into cellular biocatalytic networks. The molecularly imprinted enzyme mimics (MIEs) containing a copper center and specific substrate binding domain, could perform highly‐specific abiotic transformation inside cells, particularly in a gain‐of‐functions. Importantly, Cu‐MIEs exclusively catalyze target substrates and retain its superb performance even in the presence of copper‐poisoning molecules like glutathione (GSH).
ISSN:1433-7851
1521-3773
1521-3773
DOI:10.1002/anie.202409849