Systems Biology Group Meeting

Presenter: James Eastwood, Ph.D. Candidate, New York University

Topic: Designing Peptoid Macrocycles to Inhibit Protein-Protein Interactions

Many biological processes are mediated by protein-protein interactions, which typically cannot be targeted by conventional small molecules. Cyclic peptoids (oligomers of N-substituted glycine) provide a scaffold for displaying chemical functional groups to target a protein surface and modulate protein-protein interactions. An eight-residue peptoid macrocycle designed to inhibit the Skp2-Cks1 complex and prevent degradation of peptide hormone p27 has shown significant recovery of p27 levels in endometrial cancer cells in preliminary trials. Future designs will benefit from several improvements being made to the Rosetta design protocol to model the flexibility of the cyclic backbone and design sequences that rigidify it.