Hewitt, SH, Filby, MH, Hayes, E et al. (4 more authors) (2017) Protein surface mimetics: understanding how ruthenium tris(bipyridines) interact with proteins. ChemBioChem, 18 (2). pp. 223-231. ISSN 1439-7633
Abstract
Protein surface mimetics achieve high affinity binding by exploiting a scaffold to project binding groups over a large area of solvent exposed protein surface to make multiple co-operative non-covalent interactions. Such recognition is a pre-requisite for competitive/ orthosteric inhibition of protein-protein interactions (PPIs). This paper describes biophysical and structural studies on ruthenium(II) tris(bipyridine) surface mimetics that recognize cytochrome (cyt) c and inhibit the cyt c/ cyt c peroxidase (CCP) PPI. Binding is electrostatically driven, with enhanced affinity achieved through enthalpic contributions thought to arise from the ability of the surface mimetics to make a greater number of non-covalent interactions with surface exposed basic residues on cyt c in comparison to CCP. High field natural abundance 1H-15N HSQC NMR experiments are consistent with surface mimetics binding to cyt c in similar manner to CCP. This provides a framework for understanding recognition of proteins by supramolecular receptors and informing the design of ligands superior to the protein partners upon which they are inspired.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | This is the peer reviewed version of the following article: Hewitt, S. H., Filby, M. H., Hayes, E., Kuhn, L. T., Kalverda, A. P., Webb, M. E. and Wilson, A. J. (2016), Protein surface mimetics: understanding how ruthenium tris(bipyridines) interact with proteins. ChemBioChem. doi:10.1002/cbic.201600552; which has been published in final form at https://doi.org/10.1002/cbic.201600552. This article may be used for non-commercial purposes in accordance with the Wiley Terms and Conditions for Self-Archiving. |
Keywords: | Protein-protein interactions * receptors * supramolecular chemistry * molecular recognition * protein surface recognition |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) > NMR (Leeds) The University of Leeds > Faculty of Engineering & Physical Sciences (Leeds) > School of Chemistry (Leeds) > Organic Chemistry (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 01 Dec 2016 11:43 |
Last Modified: | 17 Nov 2017 01:38 |
Published Version: | https://doi.org/10.1002/cbic.201600552 |
Status: | Published |
Publisher: | Wiley-VCH Verlag |
Identification Number: | 10.1002/cbic.201600552 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:108838 |
Commentary/Response Threads
- Hewitt, SH, Filby, MH, Hayes, E, Kuhn, LT, Kalverda, AP, Webb, ME and Wilson, AJ Protein surface mimetics: understanding how ruthenium tris(bipyridines) interact with proteins. (deposited 01 Dec 2016 11:43) [Currently Displayed]