Rational design and optimization of cell-permeable peptidic degraders
Jakob Fuhrmann
Senior Principal Scientist, Genentech
The development of proximity-induced degraders still poses several challenges, including their relatively low cell permeability as well as high degree of conformational flexibility due to the presence of flexible linker elements. I will present our strategy to identify conformationally constrained degraders using a peptidic, macrocyclic scaffold that allows for rapid diversification. In addition, I will further highlight our lead optimization approach including ternary complex stabilization as well as property-based optimizations to generate in vivo active peptidic degraders.
Jakob received his PhD in molecular/structural biology from the University of Vienna, Austria. Thereafter, he performed his postdoctoral training in chemistry at the Scripps Research Institute, supported by an Erwin Schroedinger fellowship and EMBO long term fellowship. Jakob is currently a Senior Principal Scientist at Genentech in South San Francisco, where he manages a chemical biology lab in the field of peptide and peptidomimetic drug discovery. He has extensive experience working on constrained peptides, structure-guided designs as well as property-based lead optimization.