Technology Platform

Proteros has developed best-in-class enabling platforms and proprietary technologies for structure accelerated lead discovery. This includes production of high quality proteins, Assays and Biophysics for compound profiling and Protein Crystallography together with structure guided Medicinal Chemistry.

High Quality Protein Production

  • A company of 30 outstanding scientists with expert teams dedicated to protein/protein complexes, kinases, proteases, protein re/folding, epigenetic targets, membrane proteins and antibodies.
  • Rational Design of constructs based on 15 years experience across all target classes including post translational modifications and labeling (eg/ 15N, 13C, Se-Met, Fluorophors, Biotin).
  • Expression platform for mammalian, insect cells, E coli and yeast fermentation.
  • Industrialized purification process allowing more than 25 multistep chromatography purifications in parallel from milligram to gram scale.
  • Quality control for fitness for purpose including batch specific crystallization, activity analysis, stability testing and endotoxin levels.

Assays & Biophysics

  • Capability to screen up to 200,000 compound libraries
  • State of the art platform for enzymatic assays
  • Proprietary Reporter Displacement Assay (RDA)
    • High throughput mix-and-read binding assay based on reporter probes binding to a specific site of interest and emitting an optical signal. Upon compound addition, the rate of probe displacement is monitored over time and parameters such as Kd, kon, koff can be quantified. The assay is performed in a 384 well plate enabling the measurement of up to 3000 kinetics per day at Proteros. This assay is applicable to enzymes, protein-protein complexes, membrane proteins and biologics.
  • Applications of RDA
    • Time resolved library screening for immediate identification of fast and slow binding compounds
    • High throughput kinetic profiling delivering Kd, kon, koff, residence time
    • High throughput thermodynamic profiling by Kd quantification at different temperatures followed by Van’t Hoff analysis delivering ΔH (enthalpy) and ΔS (entropy) values. Proteros can profile 60 compounds a day with only 100 μg of protein.
  • High precision thermodynamic profiling using Isothermal Titration Calorimetry (ITC) delivering ΔH (enthalpy), ΔS (entropy) values. Due to the high protein consumption, up to 1mg per compound, Proteros‘ ability to produce large amounts of high quality proteins is the main prerequisite for ITC measurements.
  • Thermo stability analysis for compound screening, orthogonal screening and compound profiling.

Protein Structure Analysis

  • A team of 13 crystallographers with expertise in solving protein-fragment-structures, protein-ligand-structures, de novo structures and structures of biological complexes. In total, structures of over 300 different targets have been solved.
  • Commercial and customized crystallization screens of up to 2,500 conditions for each protein-ligand combination and automated imaging systems for continuous recording of crystallization events are routinely deployed.
  • With a Rigaku FR-E+ SuperBright™ in house, and ownership of a beamline at the Swiss Light Source (SLS) Proteros has access to the brightest X-ray sources.
  • Highly automated workflow for X-ray data processing
  • The FMS Proteros' Free Mounting System™ (FMS™) has been specifically designed to enable the optimization of diffraction characteristics of protein crystals. This is achieved by controlling the water content of a freely mounted crystal (without surrounding liquid) through precise regulation of the humidity in the air stream surrounding the crystal. By changing the humidity, the corresponding change in the diffraction pattern of the crystal is monitored online with X-rays.
  • Additional applications of FMS applied to projects to increase success rates
    • FMS-Laser applies defined heat cycles and thus has broadened the applicability of FMS for diffraction optimization
    • FMS-Picodropper applies small nano liter drops of Ligand solution onto the crystal surface to improve occupancy of Ligands with poor solubility
    • FMS-Evaporator to supplement crystals with organic solvents during dropping for better Ligand solubility
    • FMS-cryo switch to gently freeze crystals at optimum state directly without cryo reagent