Curk, T, Dubacheva, GV, Brisson, AR et al. (1 more author) (2022) Controlling Superselectivity of Multivalent Interactions with Cofactors and Competitors. Journal of the American Chemical Society, 144 (38). pp. 17346-17350. ISSN 0002-7863
Abstract
Moieties that compete with multivalent interactions or act as cofactors are common in living systems, but their effect on multivalent binding remains poorly understood. We derive a theoretical model that shows how the superselectivity of multivalent interactions is modulated by the presence of cofactors or competitors. We find that the role of these participating moieties can be fully captured by a simple rescaling of the affinity constant of the individual ligand–receptor bonds. Theoretical predictions are supported by experimental data of the membrane repair protein annexin A5 binding to anionic lipid membranes in the presence of Ca2+ cofactors and of the extracellular matrix polysaccharide hyaluronan (HA) binding to CD44 cell surface receptors in the presence of HA oligosaccharide competitors. The obtained findings should facilitate understanding of multivalent recognition in biological systems and open new routes for fine-tuning the selectivity of multivalent nanoprobes in medicinal chemistry.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2022 The Authors. Published by American Chemical Society. This is an author produced version of an article published in the Journal of the American Chemical Society. Uploaded in accordance with the publisher's self-archiving policy. |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) |
Funding Information: | Funder Grant number EU - European Union GA 306435 |
Depositing User: | Symplectic Publications |
Date Deposited: | 05 Apr 2023 14:51 |
Last Modified: | 14 Sep 2023 00:13 |
Status: | Published |
Publisher: | American Chemical Society |
Identification Number: | 10.1021/jacs.2c06942 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:190894 |