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Design and synthesis of Nrf2-derived hydrocarbon stapled peptides for the disruption of protein-DNA-interactions

PLoS ONE, ISSN: 1932-6203, Vol: 17, Issue: 6 June, Page: e0267651
2022
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Article Description

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.

Bibliographic Details

Bianca Wiedemann; Dominic Kamps; Laura Depta; Jörn Weisner; Jana Cvetreznik; Stefano Tomassi; Sascha Gentz; Jan-Erik Hoffmann; Matthias P. Müller; Oliver Koch; Leif Dehmelt; Daniel Rauh; Alessio Lodola

Public Library of Science (PLoS)

Multidisciplinary

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