With a state-of-the-art biophysical analysis platform, CD BioSciences offers clients professional technical support for structural biology and biophysical characterization. We have the strength to customize hit identification and characterization methods for specific protein-protein interactions (PPIs) for our clients, providing new avenues for drug development.

Background

Advances in the understanding of disease mechanisms are helping to dissect complex and multifactorial systems to identify reliable, safe and effective drugs. The origins of disease are often in complex networks of biological interactions that need to be understood not only at the clinical level but also at the phenotypic and molecular levels. Protein-protein interactions (PPIs) are central to all biological processes and the number of PPIs in the human proteome is estimated to be around 400,000. Therefore, PPIs are regarded as an attractive pool of largely unexplored target space for the development of new therapies.

The regulation of PPIs represents an attractive approach for the treatment of a range of diseases. As the complexity of PPI epitopes increases, regulation becomes increasingly challenging. Recent advances in PPI modulators (PPIMs) research have shown that PPIs across all epitope classes can be modulated using small molecules, peptides or peptidomimetics. Currently, specialized hit identification and characterization methods have been developed to determine the starting point for drug discovery efforts. It is clear that therapeutic interventions by PPIMs open up exciting new horizons for future drug development.

Fig.1 Mechanisms of PPI modulation. (Walse, 2017)

Our Services

Our researchers have developed a variety of sensitive methods to reliably identify high-quality starting hits. Our advances in technologies such as high-throughput X-ray crystallography, biophysical screening and computational chemistry will improve the success of our clients' PPI screening campaigns. We offer services including but not limited to:

• Structure determination of protein-protein complexes.
• Characterization of protein-protein interfaces.
• Identification of binding cavities and "hot spots" for small molecules, peptides, or peptidomimetics.
• Assessment of druggability.
• Identification of PPIs using MS-based proteomics.
• Screen large compound libraries in high-throughput screens and for hit validation.
• determination of PPIM kinetic parameters.
• localization of small-molecule inhibitors bound to protein complexes.

Our Screening and Validation Techniques for Characterization of PPIs and PPIMs

Applications

• Study on the molecular mechanism related to the PPI network.
• Provide direct clues for fragment-based drug design.
• Development of PPIMs against a number of clinically important targets.

With a dedicated research team and state-of-the-art laboratory facilities, CD BioSciences has established an advanced biophysical technology platform. We provide our clients with services for PPI and PPIM hit identification and verification using small-molecule, peptide and in silico-based strategies. If you are interested in our services, please contact us for more details.

Reference

1. Walse, B.; et al. Tailoring hit identification and qualification methods for targeting protein-protein interactions. Applied Biophysics for Drug Discovery. 2017.

• Drug Design Based on X-ray Crystallography
• Thermodynamic Characterization of Biomolecular Interactions
• Target Binding Analysis by HDX-MS
• Binding Affinity Measurement by MST
• Protein Stability Evaluation by TSA
• Fragment Screening Based on WAC
• Hit Identification by NMR-based Techniques
• Measurement of Ligand Binding Kinetics
• Identification of Small-Molecule Aggregation
• Analysis of Free Energy Calculations
• Modeling of Scaffold Hopping Transformations
• Cellular Imaging Service for Drug Discovery
• AFM-Based Biophysical Analysis of Drugs