GPCR Ligand Screening Services
Many efforts have been undertaken in academia and industry to find new ligands that can alter the activity of a specific GPCR and be used as lead molecules for drug development since GPCRs are the most common family of therapeutic targets. GPCR ligand screening services are provided by Creative Biolabs using a variety of experimental methodologies, such as assays based on cell signaling, stability, and binding. Both binding-based and signaling/activity-based assays are used in GPCR ligand screening in a simultaneous or sequential fashion since the combined application of complementary methods would lower the overall rates of false-positive and false-negative results.
GPCR Ligand Screening Services in Creative Biolabs
- Binding-based Ligand Screening Services
Although it is still a very difficult endeavor, accurately predicting the binding affinities of ligands to their biological targets is crucial to structure-based drug design. Independent of their impact on the function of the protein, binding-based tests focus exclusively on the ligands' ability to bind to the target protein. Small libraries are often the target audience for binding-based assays because they typically need more time and materials than competition-based screens due to their biophysical nature. Binding-based techniques are also employed in later stages of drug discovery, including hit validation, optimization, and lead optimization, as well as for difficult orphan targets. Surface plasmon resonance (SPR) offers numerous high-throughput formats and is a particularly sensitive way to track binding between two species in real-time. In addition, TR-FRET, ALIS, MST, and MS are also widely used to screen for ligands.
- Stability-based Ligand Screening Services
Because therapeutic proteins are inherently unstable both chemically and physically, formulating them remains a difficulty. Differential scanning fluorimetry (DSF) is one of the in vitro label-free protein stability tests that has grown in popularity, partly because of its ease of use and inexpensive instrument requirements. In a polar environment, like an aqueous solution, an external probe fluorophore with a low fluorescence signal is added. The basis of DSF is watching the fluorescence signal increase when the dye enters more nonpolar environments after protein denaturation. Comparing DSF to differential scanning calorimetry (DSC), the gold standard for protein stability, reveals numerous advantages. Although DSC has a restricted throughput, it can offer excellent information about the interactions between proteins and other compounds as well as protein temperature stability.
Fig.1 Typical DSC thermogram.1
Numerous technologies are available for the purpose of GPCR ligand screening. The most crucial factor in choosing one is coming up with a treatment hypothesis and creating the appropriate screen to look for it. All assays have their limitations, too, so it's important to create secondary assays that offer a deeper understanding of the mechanisms of action and counterassays to eliminate chemicals that act in ways that are undesirable. To satisfy various client needs, Creative Biolabs provides GPCR ligand screening services utilizing a range of experimental techniques. Please contact us for more information.
Reference
- Gooran, et al.; "Fluorescence-Based Protein Stability Monitoring—A Review." International Journal of Molecular Sciences 25.3 (2024): 1764.
