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dc.contributor.authorHartman, Alwin M
dc.contributor.authorElgaher, Walid A M
dc.contributor.authorHertrich, Nathalie
dc.contributor.authorAndrei, Sebastian A
dc.contributor.authorOttmann, Christian
dc.contributor.authorHirsch, Anna K H
dc.date.accessioned2020-08-04T13:38:51Z
dc.date.available2020-08-04T13:38:51Z
dc.date.issued2020-02-28
dc.identifier.citationACS Med Chem Lett. 2020;11(5):1041-1046. Published 2020 Feb 28. doi:10.1021/acsmedchemlett.9b00541.en_US
dc.identifier.issn1948-5875
dc.identifier.pmid32435423
dc.identifier.doi10.1021/acsmedchemlett.9b00541
dc.identifier.urihttp://hdl.handle.net/10033/622382
dc.description.abstractProtein-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.en_US
dc.language.isoenen_US
dc.publisherAmerican Chemical Society (ACS)en_US
dc.relationinfo:eu-repo/grantAgreement/EC/H2020/757913en_US
dc.rightsembargoedAccessen_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleDiscovery of Small-Molecule Stabilizers of 14-3-3 Protein-Protein Interactions via Dynamic Combinatorial Chemistry.en_US
dc.typeArticleen_US
dc.contributor.departmentHIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.en_US
dc.identifier.journalACS medicinal chemistry lettersen_US
dc.source.volume11
dc.source.issue5
dc.source.beginpage1041
dc.source.endpage1046
dc.source.journaltitleACS medicinal chemistry letters
dc.source.countryUnited States


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