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Rapid Screening of a Cell-based Assay for GLP-1 Receptor Using a Natural Product Library


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January 14, 2013

Authors: Brad Larson and Peter Banks, BioTek Instruments, Inc., Winooski, Vermont; Nicolas Pierre, Suzanne Graham, Jean-Luc Tardieu and Francois Degorce, Cisbio US, Inc., Bedford, Massachusetts





Glucagon-like peptide-1 receptor (GLP-1R) is a G-protein coupled receptor that is present in insulin-secreting beta cells. Intact GLP-1(1-37) is produced by posttranslational processing of proglucagon precursor and converted into active forms of GLP-1 [(7-36) amide and (7-37)] with N-terminal truncation. Then, active forms of GLP-1 are deactivated by the further fragmentation with peptidases1,2.

Its defining action is augmentation of glucose-induced insulin secretion following intake of carbohydrates and lipids. It also inhibits glucagon secretion and food intake. For this reason, GLP-1R is an interesting target for type-2 diabetes intervention.

Here we will demonstrate the detection of GLP-1R binding through the incorporation of a homogeneous cell-based binding assay using Tag-lite® technology. The assay was automated using a non-contact liquid dispenser commonly used in highthroughput settings. Detection of the two fluorescent emissions was accomplished simultaneously using the matched PMTs of an HTS multi-mode microplate reader. Optimization experiments were performed to validate the proper conditions to use for automated assay processing. A small primary screen of natural products was then performed under high throughput screening conditions, followed by the creation of dose-response curves using known GLP-1R binders.