Perfluoroarene-based peptide macrocycles that inhibit the Nrf2/Keap1 interaction

Steel, Richard J., O'Connell, Maria A. and Searcey, Mark (2018) Perfluoroarene-based peptide macrocycles that inhibit the Nrf2/Keap1 interaction. Bioorganic & Medicinal Chemistry Letters, 28 (16). pp. 2728-2731. ISSN 0960-894X

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Abstract

The Nrf2/Keap1 interaction is a target in the development of new therapeutic agents, where inhibition of the interaction activates Nrf2 and leads to the generation of downstream anti-inflammatory effects. Peptides that mimic the β-turn in the Keap1 active site and are constrained by a disulfide bridge have high affinity for Keap1 but no intracellular activity. The introduction of a perfluoroalkyl- bridging group to constrain the peptides, coupled with glutamic acid to proline replacement leads to a new peptide with a Ki of 6.1 nM for the Nrf2/Keap1 binding interaction, although this does not translate into intracellular activity.

Item Type: Article
Uncontrolled Keywords: nrf2 or nuclear factor erythroid 2 [nf-e2]-related factor 2,keap1,protein-protein interaction,hexafluorobenzene,peptide
Faculty \ School: Faculty of Science > School of Pharmacy
Faculty of Science > School of Chemistry
Depositing User: Pure Connector
Date Deposited: 02 Mar 2018 11:30
Last Modified: 28 Mar 2020 01:23
URI: https://ueaeprints.uea.ac.uk/id/eprint/66414
DOI: 10.1016/j.bmcl.2018.03.003

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