Selection of Peptides Inhibiting p53 Function

As “Guardian of the Genome”, the p53 tumour suppressor plays a major role in determining cell fate. Mutant forms of p53 are commonly seen in cancer, and can drive tumour development through gain of function activities. The wild-type state of p53 is responsible for chemotherapy-associated side effects. Agents modulating p53 function are therefore of significant interest. We have used yeast-display to select for Avian Pancreatic Peptide (APP) derivatives that bind specifically to p53. The lead selectant shows on-target association with p53 as measured by pull-down assays, both in vitro and in cells. Furthermore, it is able to inhibit the activity of wild-type p53 in cells. This peptide is a useful tool for disrupting p53 function and is currently being further engineered to enhance its function.