Abstract
Misregulation and mutations of the transcription factor Nrf2 are involved in the development of a variety of human diseases. In this study, we employed the technology of stapled peptides to address a protein-DNA-complex and designed a set of Nrf2-based derivatives. Varying the length and position of the hydrocarbon staple, we chose the best peptide for further evaluation in both fixed and living cells. Peptide 4 revealed significant enrichment within the nucleus compared to its linear counterpart 5, indicating potent binding to DNA. Our studies suggest that these molecules offer an interesting strategy to target activated Nrf2 in cancer cells.
Funder
German Federal ministry for Education and Research
Deutsche Forschungsgemeinschaft
European Union
German federal state North Rhine Westphalia
Publisher
Public Library of Science (PLoS)
Reference36 articles.
1. Isolation of NF-E2-related factor 2 (Nrf2), a NF-E2-like basic leucine zipper transcriptional activator that binds to the tandem NF-E2/AP1 repeat of the beta-globin locus control region;P Moi;Proceedings of the National Academy of Sciences of the United States of America
2. An Nrf2/Small Maf Heterodimer Mediates the Induction of Phase II Detoxifying Enzyme Genes through Antioxidant Response Elements;K. Itoh;Biochem Biophys Res Commun,1997
3. Role of Nrf2 in Oxidative Stress and Toxicity;Qiang Ma;Annual Review of Pharmacology and Toxicology,2013
4. NRF2 and the hallmarks of cancer;M. R. de la Vega;Cancer cell,2018
5. Modulation of proteostasis by transcription factor NRF2 and impact in neurodegenerative diseases;M. Pajares;Redox Biol,2017
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