Authors: | Wiedemann, Bianca Kamps, Dominic Depta, Laura Weisner, Jörn Cvetreznik, Jana Tomassi, Stefano Gentz, Sascha Hoffmann, Jan-Erik Müller, Matthias P. Koch, Oliver Dehmelt, Leif Rauh, Daniel |
Title: | Design and synthesis of Nrf2-derived hydrocarbon stapled peptides for the disruption of protein-DNA-interactions |
Language (ISO): | en |
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. |
Subject Headings: | Fluorescence polarization DNA electrophoresis Electrophoretic mobility shift assay HeLa cells Nucleic acids Peptide synthesis Permeability Transcription factors |
Subject Headings (RSWK): | DNA Elektrophorese Transkriptionsfaktor |
URI: | http://hdl.handle.net/2003/41010 http://dx.doi.org/10.17877/DE290R-22859 |
Issue Date: | 2022-06-22 |
Rights link: | https://creativecommons.org/licenses/by/4.0/ |
Appears in Collections: | Medizinische Chemie und Chemische Biologie |
Files in This Item:
File | Description | Size | Format | |
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journal.pone.0267651.pdf | 1.17 MB | Adobe PDF | View/Open |
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