Targeting Cell Surface Receptors with SUPR Peptides

Richard W. Roberts, Ph.D.
Professor and Chair
Department of Chemical Engineering and Material Science
University of Southern California

Natural peptides often have poor biostability and natural sequences cannot readily be converted into drug-like molecules without extensive medicinal
chemistry.  We have recently adapted mRNA display to evolve highly stable cyclic peptides while retaining function toward the intended target.  To do this, we have used a combination of chemical cyclization and an expanded genetic code to create new functional peptides.  These experiments resulted in a dramatically stabilized SUPR peptides (Scanning Unnatural Protease Resistant).  We have used this approach to target signaling proteins and the cell surface receptor Her2.  The resulting compounds have high affinity and excellent  selectivity  toward  Her2,  enabling  orthogonal  labeling  of  the receptor for imaging and therapeutic applications. 

Dr. Richard W. Roberts received his Ph.D.  in Biophysical Chemistry from Yale University  in  1993.  Dr.  Robert’s  was  a  Postdoctoral  Fellow  at  Harvard Medical  School  Department  of  Genetics/MGH  Department  of  Molecular Biology from 1993-97.  Dr. Roberts is currently Chair of the Mork Family Department of Chemical Engineering and Materials Science and a Professor of  Chemistry,  Chemical  Engineering,  and  Molecular  and  Computational Biology at the University of Southern California. Research in the Roberts lab focuses on the protein synthesis machinery both as a tool for polypeptide   
design and as a target that can be probed using chemical means. A key aspect of his lab's work is peptide and protein design using in vitro selection experiments.