Abstract: Human Pancreatic Polypeptide mutants are provided which have utility, inter alia, for regulation of energy intake or energy metabolism, control of intestinal secretion, decrease of gastrointestinal tract motility, decrease of rate of gastric emptying, treatment of obesity or overweight, or conditions in which obesity or overweight is a contributory factor.

Abstract: Use of mutated ?-arrestin for an improved enzyme complementation assay or translocation assay, the improved enzyme complementation assay comprising: i) adding a substrate to a cell comprising a GPCR-EA fusion protein and a ?-arrestin-EB fusion protein, wherein the ?-arrestin is mutated, ii) adding a ligand to obtain, if possible, a GPCR-EA/?-arrestin-EB complex, and iii) measuring a signal arising from association of EA and EB to create an enzymatically active protein catalyzing conversion of the substrate which leads to a detectable signal, wherein the improvement leads to an increased signal compared with the signal obtained by use of the same process employing a ?-arrestin-EB fusion protein, wherein the ?-arrestin is wild type ?-arrestin, and the improved ?-arrestin translocation assay comprising i) providing a cell expressing a GPCR and comprising a ?-arrestin associated with an optically detectable molecule, ODM, wherein the ?-arrestin is mutated, ii) adding a ligand to obtain, if possible, a GPCR/?-arre

Abstract: An improved BRET assay, wherein the BRET signal is enhanced and/or prolonged. The improved BRET assay comprises the steps of i) adding a substrate to a cell comprising GPCR-Rluc fusion protein and a ?-arrestin-GFP fusion protein, wherein the (?-arrestin is mutated, ii) adding a ligand to obtain, if possible, a GPCR-Rluc/(?-arrestin-GFP complex, and iii) measuring a BRET signal to obtain a BRET ratio, wherein the improvement leads to an increased BRET ratio compared with the ratios obtained by use of the same process employing a ?-arrestin-GFP fusion protein wherein the ?-arrestin is the wild type ?-arrestin, or employing a 13-arrestin-GFP fusion protein, wherein the (?-arrestin is a ?-arrestin specifically mutated so that it acts on the receptor independent of the receptors phosphorylation state. The invention further relates to a stable substrate solution for use in an improved BRET assay.

Abstract: The present invention relates to a method for identifying compounds capable of affecting the activity of G-protein coupled receptors (GPCRs), i.e. identifying agonists or antagonists of said receptor type. Such compounds are later useful e.g. as drugs or as leads in drug development. More specifically, if agonists are desired, the method comprises contacting a test compound with cell membrane from a GPCR expressing cell line, a kinase, such as G-protein coupled receptor kinase (GRK), and arrestin. If the test compound is an agonist it will allow said arrestin to bind to activated and phosphorylated GPCR. The above mentioned mixture is then contacted with carrier material capable of binding GPCRs, and signals are detected as an indication that the test compound is capable of acting as an agonist of GPCR.