Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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14-3-3 Proteins / antagonists & inhibitors*
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Dose-Response Relationship, Drug
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Fibroblasts / chemistry
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Fibroblasts / cytology
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High-Throughput Screening Assays*
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Humans
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Lung / chemistry
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Lung / cytology
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Matrix Metalloproteinase 1 / genetics
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Matrix Metalloproteinase 1 / metabolism
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Models, Molecular
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Molecular Structure
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Protein Binding / drug effects
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Small Molecule Libraries / chemistry
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Small Molecule Libraries / pharmacology*
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Structure-Activity Relationship
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Up-Regulation / genetics
Substances
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14-3-3 Proteins
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RNA, Messenger
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Small Molecule Libraries
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Matrix Metalloproteinase 1