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 N in a cellular assay.
Chemical Genomics Centre of the Max Planck Society, Otto-Hahn-Straße 15, D-44227 Dortmund, Germany.
Philipp
P
Thiel
Lars
L
Röglin
Nicole
N
Meissner
Sven
S
Hennig
Oliver
O
Kohlbacher
Christian
C
Ottmann
D048948:14-3-3 Proteins / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000737:chemistry / Q000166:cytology; D057166:High-Throughput Screening Assays; D006801:Humans; D008168:Lung / Q000737:chemistry / Q000166:cytology; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D015854:Up-Regulation / Q000235:genetics
D048948:14-3-3 Proteins; D012333:RNA, Messenger; D054852:Small Molecule Libraries; D020781:Matrix Metalloproteinase 1