Cell-Based Function Selection of Peptides for Protein-Protein Interaction Disruption and Targeted Protein Degradation
SESSION 11: PEPTIDE DESIGN AND FUNCTION
Wednesday, June 28, 2023, at 03:10 pm - 03:35 pm
SyntheX created empirical drug discovery platforms to discover protein interaction modulators. ToRPPIDO to allow for the discovery of compounds that can disrupt a specific protein-protein interaction, PPI. ToRNeDO achieves the inverse and discovers compounds that bring an E3 ubiquitin ligase and a neosubstrate of interest together to achieve targeted protein degradation. Using genetically engineered circuits, the platforms rely on intracellular drug selection. This allows for the unbiased discovery of compounds that can engage targets in either competitive or allosteric ways to achieve a desired mechanism of action. This intracellular approach bypasses many bottlenecks that exist with canonical in-vitro screening assays.
The platforms are modality agnostic and can be used to discover small molecules or biologics. Taking additional advantage of intracellular screening, the cells are further engineered to ribosomally produce libraries of peptides or diversified biologics. This allows for the simultaneous production and selection of potent compounds in an efficient manner while sampling billions of sequences for very specific functions. This approach results in the concurrent generation of a tool compound and the mapping of an exploitable pocket for protein interaction modulation. The platforms have generated an internal oncology pipeline focused on unique mechanisms of action around genetically validated drug targets, largely targeting crucial nodes in the Ras-MAPK pathway in novel ways.
Dr. Maria Soloveychik is the co-founder and CEO of SyntheX, a therapeutics company working on accelerating drug discovery using synthetic biology with an internal oncology pipeline. SyntheX was founded in 2016 and is based in San Francisco. Maria obtained her Ph.D. from the department of Molecular Genetics at the University of Toronto, where she discovered novel pathways linking metabolism and epigenetic signaling. Maria was previously a research scientist at a structural genomics consortium, where her work led to the determination of numerous structures and identification of several drug candidates.