The Proteros´expert team offers biochemical, biophysical and cellular profiling of ligand target interactions using state of the art and innovative technologies to support your drug discovery programs from Screen to Lead. Strategies to identify and optimize inhibitors with customized mode of inhibitions are available as well as diversity and fragment screening libraries.
By combination of Proteros´ scientific expertise within Protein Science, Protein Crystallography and Assays, Biophysics & Screening, Proteros offers structure-centric integrated DISCOVERY SERVICES for challenging targets.
Proteros´ Assay, Biophysics & Screening platform is capable to support drug discovery programs on all typical target and inhibitor families:
- Targets: Enzymes, membrane proteins, GDPRs, nuclear receptors, channels, scaffolding proteins
- Inhibitors: Fragments, small molecules, peptides and peptidomimetics, biologics
We can specifically identify and optimize compounds with desired inhibition modes, including:
- Allosteric inhibition
- PPI Inhibitors
- Covalent Inhibitors
- Extended inhibitor residence time
- Selective targeting of non activated enzyme forms
Supported by our Proteros protein crystallography department, we provide all structural information necessary for efficient mode-of-inhibition analysis and hit to lead optimization.
With fast turnaround times, we can efficiently support weekly rounds of compound optimization, by supplying multiple compound parameters as:
- Ligand binding: Kd, ΔH, ΔS, N, Tm
- Inhibition analysis: IC50, EC50, Ki
- Ligand binding kinetics: kon, koff, kinact, residence time
A full suite of Profiling Technologies to support your Integrated Drug Discovery Program. Proteros´ Assays, Biophysics & Screening expert team nominates the best possible assay technologies from the Proteros´ arsenal of enzymatic, biophysical and cellular methods to perform primary high throughput screens, subsequent hit validation/profiling and hit to lead optimization.
The RDA represents a truly high throughput binding assay. Reporter probes are designed that bind to the target site of interest. Reporter probe binding to the target leads to a specific optical signal that can be read in 384 well format. When the ligand of interest binds to the target, the reporter probe is displaced, which leads to a dose dependent loss of the reporter probe binding signal. At equilibrium, compound affinity can be determined (Kd). Monitoring the time dependent signal loss yields the compound’s binding kinetics (koff, kon and the residence time for non-covalent ligands and kinact for covalent ligands).
The RDA can be used to profile ligands as fragments, small molecules, peptide, protein-protein-interactions and biologics. Reporter probes are designed from small molecules, peptides, DNA, co-factors, protein binding partners (PPI) and biologics. The RDA can be used for soluble proteins and membrane proteins.
For more than 100 targets, the RDA is already established and can be used for library screening, affinity profiling and kinetic profiling immediately. In addition the RDA can be developed in a customized manner in short turnaround times.
For more information on our RDA based Gallery Assays please click here.
In addition to the unique RDA Proteros´ Assays, Biophysics & Screening platform comprises multiple additional, innovative and state of the art technologies, allowing a customized screening and profiling strategy for each individual drug discovery program.
SPR (Surface Plasmon Resonance; GE Healthcare) state of the art technology for library screening, affinity profiling (Kd) and kinetic profiling (kon, koff, residence time) after immobilization of the target on the surface of specialized flow channels.
Conclusion on: Ligand binding, ligand affinity, ligand binding kinetics, and protein-protein complex formation.
Advantage: Proteros uses the Biacore 8K instrument that combines the sensitivity of the T200 instrument with an increased throughput. Ligands size ranges from fragments to biologics.
ITC (Isothermal Titration Calorimetry; Malvern) state of the art, label free technology for quantification of binding affinities by monitoring the produced or consumed heat during target-ligand binding (Kd, ΔG). In addition the enthalpic and entropic binding contribution as well as the binding stoichiometry (ΔH, ΔS and N values) are quantified.
Conclusion on: Ligand binding affinity, thermodynamics and stoichiometry.
Advantage: Information rich, label free technology.
NanoDSF (Differential Scanning Fluorimetry; Nanotemper®) label and assay development free technology to detect target-ligand binding by quantification of the protein´s melting temperature (Tm). In addition nanoDSF is applied to support buffer and protein constructs optimization.
Conclusion on: Ligand binding, protein stability under various buffer conditions, protein construct stability, and the identification of ligand binding protein domains.
Advantage: Generic, label free, no assay development, applicable to soluble proteins and solubilized membrane proteins.
MST® (MicroScale Thermophoresis; Nanotemper®) technology for quantification of biomolecular interactions by monitoring the protein mobility rate along a temperature gradient in absence and presence of ligands.
Conclusion on: Ligand binding, ligand affinity, and protein-protein complex formation.
Advantage: Rapid identification of ligand binding and affinity quantification from pM to mM Kd values.
Proteros offers a hand selected 3k fragment library and two modules of high quality HTS small molecule libraries for screening applications. Depending on the target, screens can be performed with the biophysical, enzymatic or cellular technologies described above. Rapid virtual and synthetic hit expansion is facilitated by a cooperation between Proteros and the compound library provider Enamine. By combination of the screening service with our protein crystallography services, hit-target structures could be produced to analyze the hit binding mode for selection of most tractable hit classes.
Proteros can also screen your libraries with a throughput of up to 100,000 ligands per week.
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