Bifunctional Metal-Binding Scaffolds for Activation of the p53 Y220C Mutant in Cancer

The p53 protein plays a major role in cancer prevention, and over 50% of cancer diagnoses can be attributed to mutated p53. The main function of p53 is to prevent uncontrolled growth of damaged cells and inhibit tumour formation. A common mutation, Y220C, creates a cavity at the protein’s surface and causes protein unfolding. Our objective is to stabilize the mutant and restore its function. I have synthesized a series of compounds and initial cell testing concluded that our lead compounds are more cytotoxic than the front-line drug cisplatin. We plan to further investigate the ability of our compounds to induce programmed cell death in cells harbouring the Y220C mutation, and determine if this results in restoration of p53 protein function. Expected outcomes for this proposal is that we will gain insight into the mechanism of action of our compounds, allowing us to develop more efficient chemotherapeutics moving forward.

Faculty Supervisor:

Tim Storr

Student:

Partner:

Université de Strasbourg

Discipline:

Physics

Sector:

Education

University:

Simon Fraser University

Program: