Please use this identifier to cite or link to this item: doi:10.22028/D291-30923
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Title: Discovery of Small-Molecule Stabilizers of 14-3-3 Protein–Protein Interactions via Dynamic Combinatorial Chemistry
Author(s): Hartman, Alwin M.
Elgaher, Walid A. M.
Hertrich, Nathalie
Andrei, Sebastian A.
Ottmann, Christian
Hirsch, Anna
Language: English
Title: ACS medicinal chemistry letters
Volume: 11
Issue: 5
Startpage: 1041
Endpage: 1046
Publisher/Platform: ACS
Year of Publication: 2020
Publikation type: Journal Article
Abstract: Protein–protein interactions (PPIs) play an important role in numerous biological processes such as cell-cycle regulation and multiple diseases. The family of 14-3-3 proteins is an attractive target as they serve as binding partner to various proteins and are therefore capable of regulating their biological activities. Discovering small-molecule modulators, in particular stabilizers, of such complexes via traditional screening approaches is a challenging task. Herein, we pioneered the first application of dynamic combinatorial chemistry (DCC) to a PPI target, to find modulators of 14-3-3 proteins. Evaluation of the amplified hits from the DCC experiments for their binding affinity via surface plasmon resonance (SPR), revealed that the low-micromolar (KD 15–16 μM) acylhydrazones are 14-3-3/synaptopodin PPI stabilizers. Thus, DCC appears to be ideally suited for the discovery of not only modulators but even the more elusive stabilizers of notoriously challenging PPIs.
DOI of the first publication: 10.1021/acsmedchemlett.9b00541
URL of the first publication: https://pubs.acs.org/doi/10.1021/acsmedchemlett.9b00541
Link to this record: hdl:20.500.11880/29139
http://dx.doi.org/10.22028/D291-30923
ISSN: 1948-5875
Date of registration: 14-May-2020
Faculty: NT - Naturwissenschaftlich- Technische Fakultät
Department: NT - Pharmazie
Professorship: NT - Prof. Dr. Anna Hirsch
Collections:UniBib – Die Universitätsbibliographie

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