Discovery Platform

Discovering New Molecular Entities

Our programs focus on the discovery and development of peptides that enter cells and disrupt protein-protein interactions (PPI), impacting transcriptional regulation of oncogenic and immune-modulatory proteins. Sapience’s Peptide-Antagonist Discovery System (PADS) is a powerful tool to select and optimize hits against any PPI of interest.

PADS Platform

Sapience’s PADS platform is a library-based screening system that employs a protein fragment complementation-based approach. Key to this approach is that the system is performed in an intracellular environment. This means that the protein target as well as the peptide library members are expressed in live cells, ensuring that our peptide hits are more likely to be resistant to degradation by proteases, soluble, nontoxic, and target-specific in the presence of other cytoplasmic proteins. These are all attributes worth identifying as early as possible in the discovery process to save time and expense of working on hits of no value, and are not possible to assess using extracellular in vitro approaches. Our PADS platform process can be summarized as follows:

Design the Screen

  • Identify PPI of interest
  • Clone region(s)/domain(s) of protein target of interest
  • Design semi-rational multi-million-member peptide library to screen against target 

Run the Screen

  • In vitro expression system used to co-express target and library
  • Viable colonies contain target/library member complex
  • Successful campaign identifies a single ‘hit’ peptide for further development

Develop Hits into Therapeutic Leads

  • Sapience peptide chemists use hit as the scaffold to design small, rational peptide library optimizing for manufacturability, solubility, stability, immunogenicity, and activity