Tools
Tools
Steel, Richard J., O'Connell, Maria A. 
ORCID: https://orcid.org/0000-0002-0267-0951 and Searcey, Mark ORCID: https://orcid.org/0000-0003-2273-8949
(2018)
Perfluoroarene-based peptide macrocycles that inhibit the Nrf2/Keap1 interaction.
Bioorganic & Medicinal Chemistry Letters, 28 (16).
pp. 2728-2731.
ISSN 0960-894X
Preview |
PDF (Accepted manuscript)
- Accepted Version
Available under License Creative Commons Attribution Non-commercial No Derivatives. Download (664kB) | Preview |
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: | 21 Oct 2022 18:32 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/66414 |
| DOI: | 10.1016/j.bmcl.2018.03.003 |
Actions (login required)
 |
View Item |