Year: 2024
Type: article
Abstract: 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.
Source: Angewandte Chemie
Authors: Zhiguo Gao, Quanlin Shao, Jiaqi Xing, Yi Liang, Fanzhen Meng, Jian Chen, Wei He, Yaojia Li, Baiwang Sun
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: bronze
OpenAlex ID: W4401335750