A Supramolecular Stabilizer of the 14-3-3ζ/ERα Protein-Protein Interaction with a Synergistic Mode of Action
© 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA..
We report on a stabilizer of the interaction between 14-3-3ζ and the Estrogen Receptor alpha (ERα). ERα is a driver in the majority of breast cancers and 14-3-3 proteins are negative regulators of this nuclear receptor, making the stabilization of this protein-protein interaction (PPI) an interesting strategy. The stabilizer (1) consists of three symmetric peptidic arms containing an arginine mimetic, previously described as the GCP motif. 1 stabilizes the 14-3-3ζ/ERα interaction synergistically with the natural product Fusicoccin-A and was thus hypothesized to bind to a different site. This is supported by computational analysis of 1 binding to the binary complex of 14-3-3 and an ERα-derived phosphopeptide. Furthermore, 1 shows selectivity towards 14-3-3ζ/ERα interaction over other 14-3-3 client-derived phosphomotifs. These data provide a solid support of a new binding mode for a supramolecular 14-3-3ζ/ERα PPI stabilizer.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:59 |
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| Enthalten in: |
Angewandte Chemie (International ed. in English) - 59(2020), 13 vom: 23. März, Seite 5284-5287 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Gigante, Alba [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 17.03.2021 Date Revised 13.11.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/anie.201914517 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM304157864 |
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| 245 | 1 | 2 | |a A Supramolecular Stabilizer of the 14-3-3ζ/ERα Protein-Protein Interaction with a Synergistic Mode of Action |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. | ||
| 520 | |a We report on a stabilizer of the interaction between 14-3-3ζ and the Estrogen Receptor alpha (ERα). ERα is a driver in the majority of breast cancers and 14-3-3 proteins are negative regulators of this nuclear receptor, making the stabilization of this protein-protein interaction (PPI) an interesting strategy. The stabilizer (1) consists of three symmetric peptidic arms containing an arginine mimetic, previously described as the GCP motif. 1 stabilizes the 14-3-3ζ/ERα interaction synergistically with the natural product Fusicoccin-A and was thus hypothesized to bind to a different site. This is supported by computational analysis of 1 binding to the binary complex of 14-3-3 and an ERα-derived phosphopeptide. Furthermore, 1 shows selectivity towards 14-3-3ζ/ERα interaction over other 14-3-3 client-derived phosphomotifs. These data provide a solid support of a new binding mode for a supramolecular 14-3-3ζ/ERα PPI stabilizer | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a 14-3-3 | |
| 650 | 4 | |a ERα | |
| 650 | 4 | |a protein-protein interaction | |
| 650 | 4 | |a stabilizers | |
| 650 | 4 | |a supramolecular systems | |
| 650 | 7 | |a 14-3-3 Proteins |2 NLM | |
| 650 | 7 | |a Estrogen Receptor alpha |2 NLM | |
| 650 | 7 | |a Glycosides |2 NLM | |
| 650 | 7 | |a Peptides |2 NLM | |
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| 700 | 1 | |a Sijbesma, Eline |e verfasserin |4 aut | |
| 700 | 1 | |a Sánchez-Murcia, Pedro A |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Xiaoyu |e verfasserin |4 aut | |
| 700 | 1 | |a Bier, David |e verfasserin |4 aut | |
| 700 | 1 | |a Bäcker, Sandra |e verfasserin |4 aut | |
| 700 | 1 | |a Knauer, Shirley |e verfasserin |4 aut | |
| 700 | 1 | |a Gago, Federico |e verfasserin |4 aut | |
| 700 | 1 | |a Ottmann, Christian |e verfasserin |4 aut | |
| 700 | 1 | |a Schmuck, Carsten |e verfasserin |4 aut | |
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