Engineering high-affinity cyclic peptides to bind intracellular antigens

Cyclotides are tiny, cyclic plant proteins with extreme tolerance to heat, pH, and proteolysis. A select few of these proteins have the ability to cross mammalian cell membranes. The aim of this project is to combine the structural benefits of the cyclotide scaffold with the high-throughput affinity maturation capabilities of yeast surface display. This library will ultimately be used to generate ultrastable binders that can disrupt intracellular protein-protein interactions, yielding candidates for immunotherapies.