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Lookup NU author(s): Dr Tom McAllisterORCiD, Professor Akane Kawamura
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).
© 2018 The Royal Society of Chemistry. 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.
Author(s): McAllister TE, Yeh T-L, Abboud MI, Leung IKH, Hookway ES, King ONF, Bhushan B, Williams ST, Hopkinson RJ, Munzel M, Loik ND, Chowdhury R, Oppermann U, Claridge TDW, Goto Y, Suga H, Schofield CJ, Kawamura A
Publication type: Article
Publication status: Published
Journal: Chemical Science
Year: 2018
Volume: 9
Issue: 20
Pages: 4569-4578
Print publication date: 28/05/2018
Online publication date: 23/04/2018
Acceptance date: 23/04/2018
Date deposited: 14/10/2019
ISSN (print): 2041-6520
ISSN (electronic): 2041-6539
Publisher: Royal Society of Chemistry
URL: https://doi.org/10.1039/c8sc00286j
DOI: 10.1039/c8sc00286j
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