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Non-competitive cyclic peptides for targeting enzyme-substrate complexes

Lookup NU author(s): Dr Tom McAllisterORCiD, Professor Akane Kawamura

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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).

Abstract

© 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.

Publication metadata

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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