Virtual screening and experimental validation reveal novel small-molecule inhibitors of 14-3-3 protein-protein interactions

We report first non-covalent and exclusively extracellular inhibitors of 14-3-3 protein-protein interactions identified by virtual screening. Optimization by crystal structure analysis and in vitro binding assays yielded compounds capable of disrupting the interaction of 14-3-3σ with aminopeptidase...

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Bibliographic Details
Published in:Chemical communications (Cambridge, England) England), 2013-01, Vol.49 (76), p.8468-8470
Main Authors: Thiel, Philipp, Röglin, Lars, Meissner, Nicole, Hennig, Sven, Kohlbacher, Oliver, Ottmann, Christian
Format: Article
Language:English
Subjects:
14-3-3 Proteins - antagonists & inhibitors
Dose-Response Relationship, Drug
Fibroblasts - chemistry
Fibroblasts - cytology
High-Throughput Screening Assays
Humans
Lung - chemistry
Lung - cytology
Matrix Metalloproteinase 1 - genetics
Matrix Metalloproteinase 1 - metabolism
Models, Molecular
Molecular Structure
Protein Binding - drug effects
RNA, Messenger - genetics
RNA, Messenger - metabolism
Small Molecule Libraries - chemistry
Small Molecule Libraries - pharmacology
Structure-Activity Relationship
Up-Regulation - genetics
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Summary:We report first non-covalent and exclusively extracellular inhibitors of 14-3-3 protein-protein interactions identified by virtual screening. Optimization by crystal structure analysis and in vitro binding assays yielded compounds capable of disrupting the interaction of 14-3-3σ with aminopeptidase N in a cellular assay.
ISSN:1359-7345
1364-548X
DOI:10.1039/c3cc44612c