Biophysical Assay Services
LifeSensors understands that early drug discovery programs are both labor intensive and time consuming. Besides involvement of both cellular and biochemical assays, biophysical characterization of potential hits is also a vital part of the drug discovery process – from early hit finding to mechanistic profiling during lead optimization. As part of our ongoing efforts to provide customers with services to further their drug discovery processes, LifeSensors introduces our Biophysical Assay Services.
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Assays
Surface Plasmon Resonance (SPR) – A label-free optical technique for measuring interactions in real time, SPR is a powerful technology for drug discovery. A target of interest (ligand) is immobilized on a thin gold-coated glass chip while a second molecule (analyte) is flowed over the chip. Changes in the refractive index at the gold surface as the analyte binds to and dissociates from the ligand are monitored to generate sensograms, from which kon, koff, and KD can be calculated.
Thermal Shift Assay (TSA) – Also known as ThermoFluor (TF) or differential scanning fluorimetry (DSF), this assay is based on the concept that ligand binding affects protein thermal stability. The exposure of a protein’s hydrophobic patches as it melts allows for the binding of a fluorescent dye (e.g., SYPRO Orange). The quantum yield of SYPRO Orange is significantly increased upon binding these patches, allowing for fluorescent monitoring of protein unfolding. The resulting curve can be fit to find the melting temperature (Tm) at the transition midpoint. Ligand binding stabilizes the folded or unfolded state, causing a shift in Tm that can be quantified to determine binding affinity. In addition to ligand binding, the same system can be used to identify buffer conditions that promote protein stability.
Equipment
- Multiplex from surface or solution
- 32 unique addresses
- 8 flow cells with 4 addresses each
- Immobilize 32 different ligands per sensor
- Multiple sensor addressing options
- Multiplexed buffer analysis
- Both bottle and plate modes
- Ideal for protein-protein interactions
- Measure protein-ligand interactions
- Multiplex from surface or solution
- 4 unique addresses
- Ideal for protein-protein interactions
- 384-well block format for high-throughput
- Low volume assay reduces protein consumption
- Small molecule, nucleotide, and peptide binding to target proteins
- Determination of protein-protein interactions
- Evaluation of thermal stability of target protein under a range of conditions
- Detection of binding of ligands that cannot be measured enzymatically (e.g., PPI inhibitiors, E3 binders for PROTAC applications)
Applications
LifeSensors offers convenient and customizable integrated services for running biophysical characterization of client’s protein target and ligands/drug/molecule from the initial screening through hit-to-lead optimization processes; both assays are compatible for high-throughput screening. Our other services including E3 ligase, DUB and PROTAC screening can be integrated with these biophysical characterization assays.
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