scholarly journals Screening small-molecule compound microarrays for protein ligands without fluorescence labeling with a high-throughput scanning microscope

2010 ◽  
Vol 15 (1) ◽  
pp. 016018 ◽  
Author(s):  
Yiyan Fei
Keyword(s):  
Small Molecule ◽  
High Throughput ◽  
Fluorescence Labeling ◽  
Scanning Microscope ◽  
Protein Ligands ◽  
Small Molecule Compound

scholarly journals A novel high-throughput scanning microscope for label-free detection of protein and small-molecule chemical microarrays

2008 ◽  
Vol 79 (1) ◽  
pp. 013708 ◽  
Author(s):  
Y. Y. Fei ◽  
J. P. Landry ◽  
Y. S. Sun ◽  
X. D. Zhu ◽  
J. T. Luo ◽  
...  
Keyword(s):  
Small Molecule ◽  
High Throughput ◽  
Label Free ◽  
Scanning Microscope ◽  
Label Free Detection

scholarly journals Development of a Novel High-Throughput Screen and Identification of Small-Molecule Inhibitors of the Gα–RGS17 Protein–Protein Interaction Using AlphaScreen

2011 ◽  
Vol 16 (8) ◽  
pp. 869-877 ◽  
Author(s):  
Duncan I. Mackie ◽  
David L. Roman
Keyword(s):  
Small Molecule ◽  
High Throughput ◽  
Protein Interaction ◽  
High Throughput Screening ◽  
Drug Targets ◽  
Screening Method ◽  
Fold Increase ◽  
Rgs Proteins ◽  
High Throughput Screen ◽  
Protein Protein Interaction

In this study, the authors used AlphaScreen technology to develop a high-throughput screening method for interrogating small-molecule libraries for inhibitors of the Gαo–RGS17 interaction. RGS17 is implicated in the growth, proliferation, metastasis, and the migration of prostate and lung cancers. RGS17 is upregulated in lung and prostate tumors up to a 13-fold increase over patient-matched normal tissues. Studies show RGS17 knockdown inhibits colony formation and decreases tumorigenesis in nude mice. The screen in this study uses a measurement of the Gαo–RGS17 protein–protein interaction, with an excellent Z score exceeding 0.73, a signal-to-noise ratio >70, and a screening time of 1100 compounds per hour. The authors screened the NCI Diversity Set II and determined 35 initial hits, of which 16 were confirmed after screening against controls. The 16 compounds exhibited IC50 <10 µM in dose–response experiments. Four exhibited IC50 values <6 µM while inhibiting the Gαo–RGS17 interaction >50% when compared to a biotinylated glutathione-S-transferase control. This report describes the first high-throughput screen for RGS17 inhibitors, as well as a novel paradigm adaptable to many other RGS proteins, which are emerging as attractive drug targets for modulating G-protein-coupled receptor signaling.

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