Piletsky, S.A., Bedwell, T.S., Paoletti, R. et al. (6 more authors) (2022) Modulation of acetylcholinesterase activity using molecularly imprinted polymer nanoparticles. Journal of Materials Chemistry B, 10 (35). pp. 6732-6741. ISSN 2050-750X
Abstract
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2022 The Royal Society of Chemistry. This is an author-produced version of a paper subsequently published in Journal of Materials Chemistry B. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | Acetylcholinesterase; Epitopes; Molecularly Imprinted Polymers; Nanoparticles; Organophosphates; Polymers |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > Department of Chemistry (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 13 Apr 2023 13:51 |
Last Modified: | 13 Apr 2023 14:57 |
Status: | Published |
Publisher: | Royal Society of Chemistry (RSC) |
Refereed: | Yes |
Identification Number: | 10.1039/d2tb00278g |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:198120 |