Bromfield, S.M., Posocco, P., Chan, C.W. et al. (5 more authors) (2014) Nanoscale self-assembled multivalent (SAMul) heparin binders in highly competitive, biologically relevant, aqueous media. Chemical Science. pp. 1484-1492. ISSN 2041-6539
Abstract
This paper investigates small molecules that self-assemble to display multivalent ligand arrays for heparin binding. In water, the self-assembled multivalent (SAMul) heparin binder is highly competitive with the current clinical heparin reversal agent, protamine. On addition of salt, the dimensions of the self-assembled nanostructure increase. This unique feature is due to the dynamic, responsive nature of assembly, predicted using multiscale modelling and proven experimentally, enhancing heparin binding of SAMul systems relative to fixed covalent multivalent nanostructures. Conversely, the presence of serum adversely affects the heparin binding of SAMul systems relative to covalent nanostructures due to partial destabilisation of the assemblies. Nonetheless, clotting assays in human plasma demonstrate that the SAMul system acts as a functional heparin reversal agent. Compound degradation, inducing nanostructure disassembly and loss of SAMul binding, takes place over 24 hours due to ester hydrolysis-but when bound to heparin, stability is enhanced. Heparin reversal in plasma, and the therapeutically useful degradation profile, make this SAMul approach of potential therapeutic value in replacing protamine, which has a number of adverse effects when used in the clinic.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © Royal Society of Chemistry 2014. This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Chemistry (York) |
Depositing User: | Pure (York) |
Date Deposited: | 04 Feb 2016 15:29 |
Last Modified: | 02 Feb 2025 00:04 |
Published Version: | https://doi.org/10.1039/c4sc00298a |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1039/c4sc00298a |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:92609 |
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