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Title

Evolution of Molecularly Imprinted Enzyme Inhibitors: From Simple Activity Inhibition to Pathological Cell Regulation.

Authors

Xu, Jingjing; Miao, Haohan; Zou, Lihua; Tse Sum Bui, Bernadette; Haupt, Karsten; Pan, Guoqing

Abstract

Molecular imprinting represents one of the most promising strategies to design artificial enzyme inhibitors. However, the study of molecularly imprinted enzyme inhibitors (MIEIs) remains at a primary stage. Advanced applications of MIEIs for cell regulation have rarely been explored. Using a solid‐phase oriented imprinting strategy so as to leave the active site of the enzymes accessible, we synthesized two MIEIs that exhibit high specificity and potent inhibitory effects (inhibition constant at low nM range) towards trypsin and angiogenin. The trypsin MIEI inhibits trypsin activity, tryptic digestion‐induced extracellular matrix lysis and cell membrane destruction, indicating its utility in the treatment of active trypsin‐dependent cell injury. The angiogenin MIEI blocks cancer cell proliferation by suppressing the ribonuclease activity of angiogenin and decreasing the angiogenin level inside and outside HeLa cells. Our work demonstrates the versatility of MIEIs for both enzyme inhibition and cell fate manipulation, showing their great potential as therapeutic drugs in biomedicine.

Subjects

ENZYME inhibitors; CELLULAR control mechanisms; SYNTHETIC enzymes; BINDING sites; CANCER cell proliferation; MOLECULAR imprinting; HELA cells

Publication

Angewandte Chemie, 2021, Vol 133, Issue 46, p24731

ISSN

0044-8249

Publication type

Academic Journal

DOI

10.1002/ange.202106657

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