A supramolecular stabilizer of the 14-3-3ζ/ERα protein-protein interaction with a synergistic mode of action

Alba Gigante, Eline Sijbesma, Pedro A. Sánchez-Murcia, Xiaoyu Hu, David Bier, Sandra Bäcker, Shirley Knauer, Federico Gago, Christian Ottmann (Corresponding author), Carsten Schmuck

Onderzoeksoutput: Bijdrage aan tijdschriftTijdschriftartikelAcademicpeer review

2 Citaten (Scopus)
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Samenvatting

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.

Originele taal-2Engels
Pagina's (van-tot)5284-5287
Aantal pagina's4
TijdschriftAngewandte Chemie - International Edition
Volume59
Nummer van het tijdschrift13
DOI's
StatusGepubliceerd - 11 feb 2020

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