Selective Nonpeptidic Fluorescent Ligands for Oxytocin Receptor: Design, Synthesis, and Application to Time-Resolved FRET Binding Assay

2015 ◽  
Vol 58 (5) ◽  
pp. 2547-2552 ◽  
Author(s):  
Iuliia A. Karpenko ◽  
Jean-François Margathe ◽  
Thiéric Rodriguez ◽  
Elsa Pflimlin ◽  
Elodie Dupuis ◽  
...  
Keyword(s):  
Binding Assay ◽  
Oxytocin Receptor ◽  
Time Resolved ◽  
Design Synthesis ◽  
Receptor Design ◽  
Fluorescent Ligands

scholarly journals A Time-Resolved FRET Cell-Based Binding Assay for the Apelin Receptor

ChemMedChem ◽  
2017 ◽  
Vol 12 (12) ◽  
pp. 925-931 ◽  
Author(s):  
Christel Valencia ◽  
Céline Dujet ◽  
Jean-François Margathe ◽  
Xavier Iturrioz ◽  
Thomas Roux ◽  
...  
Keyword(s):  
Binding Assay ◽  
Time Resolved ◽  
Apelin Receptor

scholarly journals Design, Synthesis and Characterization of a New Series of Fluorescent Metabotropic Glutamate Receptor Type 5 Negative Allosteric Modulators

Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1532
Author(s):  
Víctor Fernández-Dueñas ◽  
Mingcheng Qian ◽  
Josep Argerich ◽  
Carolina Amaral ◽  
Martijn D.P. Risseeuw ◽  
...  
Keyword(s):  
Binding Sites ◽  
Metabotropic Glutamate Receptor ◽  
Allosteric Modulators ◽  
Design Synthesis ◽  
Metabotropic Glutamate ◽  
Animal Disease Models ◽  
Fluorescent Ligands ◽  
The Brain

In recent years, new drug discovery approaches based on novel pharmacological concepts have emerged. Allosteric modulators, for example, target receptors at sites other than the orthosteric binding sites and can modulate agonist-mediated activation. Interestingly, allosteric regulation may allow a fine-tuned regulation of unbalanced neurotransmitter’ systems, thus providing safe and effective treatments for a number of central nervous system diseases. The metabotropic glutamate type 5 receptor (mGlu5R) has been shown to possess a druggable allosteric binding domain. Accordingly, novel allosteric ligands are being explored in order to finely regulate glutamate neurotransmission, especially in the brain. However, before testing the activity of these new ligands in the clinic or even in animal disease models, it is common to characterize their ability to bind mGlu5Rs in vitro. Here, we have developed a new series of fluorescent ligands that, when used in a new NanoBRET-based binding assay, will facilitate screening for novel mGlu5R allosteric modulators.

Cell-based β2-adrenergic receptor–ligand binding assay using synthesized europium-labeled ligands and time-resolved fluorescence

2009 ◽  
Vol 392 (2) ◽  
pp. 103-109 ◽  
Author(s):  
Eija Martikkala ◽  
Mirva Lehmusto ◽  
Minna Lilja ◽  
Anita Rozwandowicz-Jansen ◽  
Jenni Lunden ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Adrenergic Receptor ◽  
Binding Assay ◽  
Ligand Binding Assay ◽  
Time Resolved Fluorescence ◽  
Receptor Ligand ◽  
Time Resolved ◽  
Β2 Adrenergic Receptor

Nonpeptide/peptide chimeric ligands for the nociceptin/orphanin FQ receptor: design, synthesis and in vitro pharmacological activity

2004 ◽  
Vol 63 (6) ◽  
pp. 477-484 ◽  
Author(s):  
R. Guerrini ◽  
G. Carra' ◽  
G. Calo' ◽  
C. Trapella ◽  
E. Marzola ◽  
...  
Keyword(s):  
Pharmacological Activity ◽  
Orphanin Fq ◽  
Design Synthesis ◽  
Receptor Design

scholarly journals Development and Applications of a Broad-Coverage, TR-FRET-Based Kinase Binding Assay Platform

2009 ◽  
Vol 14 (8) ◽  
pp. 924-935 ◽  
Author(s):  
Connie S. Lebakken ◽  
Steven M. Riddle ◽  
Upinder Singh ◽  
W. Jack Frazee ◽  
Hildegard C. Eliason ◽  
...  
Keyword(s):  
Fluorescence Lifetime ◽  
Drug Targets ◽  
Kinase Inhibitors ◽  
Binding Assay ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Kinase Assay ◽  
Time Resolved ◽  
Traditional Activity

The expansion of kinase assay technologies over the past decade has mirrored the growing interest in kinases as drug targets. As a result, there is no shortage of convenient, fluorescence-based methods available to assay targets that span the kinome. The authors recently reported on the development of a non-activity-based assay to characterize kinase inhibitors that depended on displacement of an Alexa Fluor® 647 conjugate of staurosporine (a “tracer”) from a particular kinase. Kinase inhibitors were characterized by a change in fluorescence lifetime of the tracer when it was bound to a kinase relative to when it was displaced by an inhibitor. Here, the authors report on improvements to this strategy by reconfiguring the assay in a time-resolved fluorescence resonance energy transfer (TR-FRET) format that simplifies instrumentation requirements and allows for the use of a substantially lower concentration of kinase than was required in the fluorescence-lifetime-based format. The authors use this new assay to demonstrate several aspects of the binding assay format that are advantageous relative to traditional activity-based assays. The TR-FRET binding format facilitates the assay of compounds against low-activity kinases, allows for the characterization of type II kinase inhibitors either using nonactivated kinases or by monitoring compound potency over time, and ensures that the signal being detected is specific to the kinase of interest and not a contaminating kinase.

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