McAllister, TE;
Yeh, T-L;
Abboud, MI;
Leung, IKH;
Hookway, ES;
King, ONF;
Bhushan, B;
... Kawamura, A; + view all
(2018)
Non-competitive cyclic peptides for targeting enzyme-substrate complexes.
Chemical Science
, 9
(20)
pp. 4569-4578.
10.1039/c8sc00286j.
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Abstract
Affinity reagents are of central importance for selectively identifying proteins and investigating their interactions. We report on the development and use of cyclic peptides, identified by mRNA display-based RaPID methodology, that are selective for, and tight binders of, the human hypoxia inducible factor prolyl hydroxylases (PHDs) – enzymes crucial in hypoxia sensing. Biophysical analyses reveal the cyclic peptides to bind in a distinct site, away from the enzyme active site pocket, enabling conservation of substrate binding and catalysis. A biotinylated cyclic peptide captures not only the PHDs, but also their primary substrate hypoxia inducible factor HIF1-α. Our work highlights the potential for tight, non-active site binding cyclic peptides to act as promising affinity reagents for studying protein–protein interactions.
| Type: | Article |
|---|---|
| Title: | Non-competitive cyclic peptides for targeting enzyme-substrate complexes |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1039/c8sc00286j |
| Publisher version: | https://doi.org/10.1039/C8SC00286J |
| Language: | English |
| Additional information: | Open Access Article: This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence (http://creativecommons.org/licenses/by-nc/3.0/) |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10050364 |
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