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

Philipp Thiel; Lars Röglin; Nicole Meissner; Sven Hennig; Oliver Kohlbacher; Christian Ottmann

doi:10.1039/c3cc44612c

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

Philipp Thiel, Lars Röglin, Nicole Meissner, Sven Hennig, Oliver Kohlbacher, Christian Ottmann

Research output: Contribution to Journal › Article › Academic › peer-review

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.

Original language	English
Pages (from-to)	8468-70
Number of pages	3
Journal	Chemical Commununications
Volume	49
Issue number	76
DOIs	https://doi.org/10.1039/c3cc44612c
Publication status	Published - 4 Oct 2013
Externally published	Yes

Keywords

14-3-3 Proteins
Dose-Response Relationship, Drug
Fibroblasts
High-Throughput Screening Assays
Humans
Lung
Matrix Metalloproteinase 1
Models, Molecular
Molecular Structure
Protein Binding
RNA, Messenger
Small Molecule Libraries
Structure-Activity Relationship
Up-Regulation
Journal Article
Research Support, Non-U.S. Gov't

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

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.",

keywords = "14-3-3 Proteins, Dose-Response Relationship, Drug, Fibroblasts, High-Throughput Screening Assays, Humans, Lung, Matrix Metalloproteinase 1, Models, Molecular, Molecular Structure, Protein Binding, RNA, Messenger, Small Molecule Libraries, Structure-Activity Relationship, Up-Regulation, Journal Article, Research Support, Non-U.S. Gov't",

author = "Philipp Thiel and Lars R{\"o}glin and Nicole Meissner and Sven Hennig and Oliver Kohlbacher and Christian Ottmann",

year = "2013",

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doi = "10.1039/c3cc44612c",

language = "English",

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T1 - Virtual screening and experimental validation reveal novel small-molecule inhibitors of 14-3-3 protein-protein interactions

AU - Thiel, Philipp

AU - Röglin, Lars

AU - Meissner, Nicole

AU - Hennig, Sven

AU - Kohlbacher, Oliver

AU - Ottmann, Christian

PY - 2013/10/4

Y1 - 2013/10/4

N2 - 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.

AB - 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.

KW - 14-3-3 Proteins

KW - Dose-Response Relationship, Drug

KW - Fibroblasts

KW - High-Throughput Screening Assays

KW - Humans

KW - Lung

KW - Matrix Metalloproteinase 1

KW - Models, Molecular

KW - Molecular Structure

KW - Protein Binding

KW - RNA, Messenger

KW - Small Molecule Libraries

KW - Structure-Activity Relationship

KW - Up-Regulation

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1039/c3cc44612c

DO - 10.1039/c3cc44612c

M3 - Article

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SN - 1359-7345

VL - 49

SP - 8468

EP - 8470

JO - Chemical Commununications

JF - Chemical Commununications

IS - 76

ER -

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

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Keywords

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