Surface Plasmon Resonance (SPR) allows the profiling of biomolecular interactions between ligands (e.g. small molecules or antibodies) and targets (e.g. proteins or nucleic acids), and is a standard technique used extensively in the early drug discovery process from fragment screening to hit prioritisation and lead optimisation.
SPR is a label free biophysical technique in which a molecular target, typically a macromolecule such as a protein or nucleic acid, is immobilised to the surface of a gold sensor chip. A second molecule in solution, such as a drug compound, is then passed over the surface and binding to the target results in changes in the refractive index for light reflected on the underside of the sensor surface. This provides a powerful technique for monitoring real time interactions and establishing the kinetics of ligand binding - association and dissociation rates (ka, kd), and the equilibrium dissociation constant (KD).
At BioAscent, we have extensive experience of developing new SPR assays, or transferring existing assays from clients. These assay are used to profile the affinity of molecular interactions in order to:
screen low molecular weight fragment libraries (including our in-house fragment library) against your biological target of interest.
employ SPR (or alternative biophysical techniques) as an orthogonal assay in hit confirmation and characterisation to confirm direct target engagement.
employ SPR (or alternative biophysical techniques) as a primary or orthogonal assay to drive design make test cycles in hits-to-lead and lead optimisation.
better inform the selection of candidate molecules by understanding how their kinetic profile is likely to impact upon PK/PD relationships and selectivity over closely related anti-targets.
characterise and profile therapeutic antibodies.
Biomolecular interaction analysis, especially SPR, is used increasingly in drug development to characterise the affinity of binding between biological targets (e.g. proteins or nucleic acids) and drugs, antibodies and antigens or any series of interacting molecules. This information can be used to drive chemistry optimisation efforts in drug development or rationalise or model the behaviour of drugs in complex non-equilibrium in vivo settings.
What are the benefits of using Surface Plasmon Resonance (SPR)?
The data generated using SPR can be highly valuable at any stage of the drug discovery pipeline. At BioAscent we use it both as a standalone technique for answering discreet project questions, and as a key component to enable success in fully integrated drug discovery projects.
BioAscent currently has two state-of-the-art Biacore 8k SPR systems which are the industry standard and provide both very high-throughput and highly sensitive testing. The expertise in the team, combined with the capabilities of these instruments, allows us to develop and transfer a wide array of assays. These are used for profiling high affinity target/small molecule interactions, screening low molecular weight fragment libraries, including our own, characterising therapeutic antibodies and studying complex, multi-component interactions such as ternary complexes, which are important to profile when we are developing heterobifunctional molecules such as PROTACs.
BioAscent utilises a number of alternative approaches that can be used for biophysical screening including Thermal Shift and Microscal Thermophoresis. The team also uses Dynamic Mass Redistribution technology for GPCR targets. These approaches are often complementary to SPR.
A paper published by the team as part of the IMI, looks at how Microscale Thermophoresis is used to characterise hits from high-throughput screening. View paper.
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