Ligands for diverse protein surfaces: Design, discovery, and phenotype

ORGN 259

Alanna Schepartz, alanna.schepartz@yale.edu, Department of Chemistry, Yale University, 225 Prospect St., New Haven, CT 06520
Transient interactions between protein surfaces guide virtually every cell signaling event, and the discovery of molecules that inhibit protein-protein interactions is a foremost goal of chemical biology. This goal is complicated by the reality that protein-protein interaction domains are large, shallow, and (especially for transient complexes) closely resemble non-interacting regions of the protein exterior. This lecture will describe our work using miniature proteins and ß-peptide foldamers to recognize protein surfaces with high affinity and specificity and inhibit the formation of protein-protein interactions in vitro and in vivo. We will focus in particular on molecules that possess paralog specificity – the ability to discriminate their prescribed target from structurally related family members.