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Modulation of acetylcholinesterase activity using molecularly imprinted polymer nanoparticles

journal contribution
posted on 2022-06-10, 15:51 authored by Sergey A Piletsky, Thomas S Bedwell, Rachele Paoletti, Kal Karim, Francesco Canfarotta, Rachel Norman, Donald JL Jones, Nicholas W Turner, Elena Piletska
Modulation of enzyme activity allows for control over many biological pathways and while strategies for the pharmaceutical design of inhibitors are well established; methods for promoting activation, that is an increase in enzymatic activity, are not. Here we demonstrate an innovative epitope mapping technique using molecular imprinting to identify four surface epitopes of acetylcholinesterase (AChE). These identified epitopes were then used as targets for the synthesis of molecularly imprinted nanoparticles (nanoMIPs). The enzymatic activity of AChE was increased upon exposure to these nanoMIPs, with one particular identified epitope nanoMIP leading to an increase in activity of 47× compared to enzyme only. The impact of nanoMIPs on the inhibited enzyme is also explored, with AChE activity recovering from 11% (following exposure to an organophosphate) to 73% (following the addition of nanoMIPs). By stabilizing the conformation of the protein rather than targeting the active site, the allosteric nature of MIP-induced reactivation suggests a new way to promote enzyme activity, even under the presence of an inhibitor. This method of enzyme activation shows promise to treat enzyme deficiency diseases or in medical emergencies where an external agent affects protein function.

History

Citation

J. Mater. Chem. B, 2022, DOI https://doi.org/10.1039/D2TB00278G

Author affiliation

Department of Cardiovascular Sciences, University of Leicester

Version

  • AM (Accepted Manuscript)

Published in

Journal of Materials Chemistry B

Publisher

Royal Society of Chemistry

issn

2050-750X

eissn

2050-7518

Acceptance date

2022-03-25

Copyright date

2022

Available date

2022-06-10

Spatial coverage

England

Language

English

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