UC San Diego

Despite advances in proteomics techniques, the rational discovery of non-degrader molecular glues and their targets remains challenging. In Chapter 1, I describe the BioTAC system, an unbiased ligand-guided proximity labeling method, and showcase its ability to robustly identify small molecule targets and interactomes, including complex partners of non-degrader molecular glues. In Chapter 2, I present a detailed method development guide to implementing the BioTAC system for compounds and proteins of interest. In Chapter 3, I develop a chemoproteomics-based pipeline to identify new covalent ligand-protein binding sites for structure-interactome relationship studies, and characterize a reactive cysteine-containing hub protein as an amenable target for non-degrader molecular glue development.