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Protein Sciences

Utilizing state-of-the-art methodologies in protein production, biophysics  and structural biology to facilitate structure-based drug discovery, screening and protein characterization.

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Why Arctoris?

Hit-to-Lead workflow

  • State-of-the-art biophysical tools for high-throughput compound library screens
  • Hit validation using orthogonal biophysical/ biochemical workflows
  • Identification of binding sites using X-ray crystallography (PanDAA)
  • Refined crystal structure to define SAR and inform compound design & optimization

High-throughput screening of therapeutic target proteins

  • Unique analytics based workflows for biophysical characterization of monoclonal antibodies, bispecific antibodies, and nanobodies (mAbs/ BsAbs/ nbs) and various therapeutic target proteins
  • Early determination of binding affinity, thermostability and aggregation profile allow for robust, up-front decision making
  • 96-well based expression and purification platform allows for faster decision making with rapid turnaround times

Seamless integration of multiple disciplines

  • Gene to Protein services for biochemical / biophysical studies
    • State of the art facility at Harwell Research Complex for (RcCaH) and Diamond Light Source (DLS)
    • Gene design – protein expression & purification (small scale to large scale)
    • QC – identification and confirmation of the protein state and stability
  • Gene to structure (X-ray crystallography/ Cryo-EM)
    • Protein/ protein-ligand structure generation
    • High resolution data for the target protein
    • Structure based Drug Design (SBDD)
    • World class synchrotron facility access (Diamond Light Source)
    • Cryo-EM method of choice for large proteins or protein complexes

What can Arctoris do?

Our capabilities and assays

Protein Production

Protein expression, purification and bio-conjugation
  • Established expression platform optimized for your protein
  • High quality, assay-ready proteins with comprehensive QC (Mass spectrometry (MS), Analytical size-exclusion chromatography (aSEC), Thermostability/ Dynamic light scattering ( DLS)
  • Bioconjugation of proteins with optimized tags for downstream assays

Structural Biology

Physical quantification of protein structure and interactions with ligands
  • High-throughput robotic crystallization platform with access to Diamond Light Source
  • High-throughput fragment soaking platform
  • Outstanding experience across multiple protein classes from membrane proteins to biologics

Biophysics

Characterization of molecular interactions
  • Protein aggregation, oligomeric status, KD, on-,off-rates, ΔH
  • High-throughput ligand screening using orthogonal technologies, kinetic analysis of top hits, EC50 determination and sample purity analysis
  • Full suite of biophysical techniques available

How do we deliver?

Construct design
  • Gene constructs designed in alignment with downstream structural/ biophysical/ biochemical applications
  • Diverse tagging strategies to improve expression issues and purification

Protein expression
  • Established expression platforms for soluble, secreted and membrane proteins, mAbs and bispecific antibodies, proteins from inclusion bodies (refolding)
  • E. coli, mammalian, insect, BacMam & cell-free expression platforms
  • Small scale expression followed by analytical screening to identify best candidates for large scale prep
  • Large-scale expression (100lt/week)

Protein purification
  • High-throughput small-scale purification to determine best purification conditions (DoE/ Design of Experiment)
  • Large scale protein purification using different affinity techniques such as Immobilized metal affinity chromatography (IMAC)/ Cleavage/ sub-IMAC/ Ion Exchange Chromatography (IEX)/ Size Exclusion Chromatography (SEC)
  • QC analysis of purified protein (SDS-PAGE, differential scanning fluorimetry (DSF),Dynamic light scattering (DLS), analytical size exclusion chromatography (aSEC), Mass Spectrometry (MS), Peptide mass fingerprinting (PMF)

Bioconjugation
  • Enzyme catalyzed ligation of modified peptides/oligos (biotinylated/ fluorescent/ oligos/ peptide-oligo conjugates)
  • In vivo and in vitro biotinylation of proteins
Drug Discovery
  • High-throughput screening and identification from 5.5K fragment library (GCI/ SPR/ nanoDSF)
  • Hit characterization (affinity, Kon, Koff, thermodynamics (ITC/ SPR/ GCI)

Protein interaction analysis
  • Ligand competition assays (GCI/ SPR)
  • Protein stability analysis (buffer screen, nanoDSF)

Monoclonal/ multispecific antibody development studies
  • HT clone ranking from Cell Culture Supernatant (off-rate screening) (GCI/ SPR)
  • Affinity and avidity determination (GCI/ SPR)
  • Thermostability in buffers with excipients (nanoDSF)
  • Forced degradation studies (SEC-MALS, Mass Photometry, FidaBio)
Protein crystallization & initial screening
  • Sitting drop vapor diffusion
  • Hanging drop
  • Lipidic Cubic Phase (LCP)
  • Microbatch

Optimization & generation of diffractable crystals
  • Apo crystals
  • Co-crystals
  • Lipidic Cubic Phase (LCP)
  • Protein-protein/ antibodies/ nanobodies

Crystals mounting, X-ray screening and data collection
  • Molecular replacement (MR)
  • Multiple isomorphous replacement (MIR)
  • Multiple wavelength anomalous dispersion (MAD)

Data analyses and and structure determination
  • Phase determination
  • Model Building and refinement
  • Structure guided ligand design/ protein engineering