Miniature Protein Inhibitors of the p53–hDM2 Interaction

Abstract

Small but perfectly formed. A library of miniature protein variants was constructed that presented the minimal recognition epitope of the human double-minute 2 oncoprotein (hDM2), which was derived from the activation domain of p53 (p53AD). This library was optimized (see scheme) to yield several miniature proteins with robust folds and nanomolar affinity for hDM2. The inhibitory activities of these miniature proteins correlated with the stability of the protein fold. This emphasizes the benefit of presenting the p53AD epitope on a miniature protein scaffold.