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Non-competitive cyclic peptides for targeting enzyme-substrate complexes

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. Green open access

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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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