Svenningsen, S.W., Luige, O. orcid.org/0000-0002-1448-5630, Abdulkarim, Z. et al. (2 more authors) (2024) Zinc N,N-bis(2-picolyl)amine chelates show substitution-dependent cleavage of phosphodiesters in models as well as of PNAzyme-RNA bulges. Molecules, 29 (9). 2123. ISSN 1420-3049
Abstract
PNAzymes are a group of artificial enzymes which show promising results in selective and efficient cleavage of RNA targets. In the present study, we introduce a series of metal chelating groups based on N,N-bis(2-picolyl) groups (parent, 6-methyl and 6-amino substituted) as the active sites of novel PNAzymes. An improved synthetic route for the 6-amino analogues is described. The catalytic activity of the chelating groups for cleaving phosphodiesters were assessed with the model substrate 2-hydroxypropyl p-nitrophenyl phosphate (HPNPP), confirming that the zinc complexes have the reactivity order of parent < 2-methyl < 2-amino. The three ligands were conjugated to a PNA oligomer to form three PNAzymes which showed the same order of reactivity and some sensitivity to the size of the RNA bulge designed into the catalyst–substrate complex. This work demonstrates that the kinetic activity observed for the model substrate HPNPP could be translated onto the PNAzymes, but that more reactive Zn complexes are required for such PNAzymes to be viable therapeutic agents.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
Keywords: | PNAzyme; RNA bulge; RNA substrate; metal chelate; phosphodiester cleavage; Zinc; Peptide Nucleic Acids; Chelating Agents; RNA; Catalysis; Amines; Kinetics; Organophosphates |
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: | 28 May 2024 11:03 |
Last Modified: | 28 May 2024 11:03 |
Published Version: | http://dx.doi.org/10.3390/molecules29092123 |
Status: | Published |
Publisher: | MDPI AG |
Refereed: | Yes |
Identification Number: | 10.3390/molecules29092123 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:212805 |