Cyclic Peptide-Based Probes for Matrix Metalloproteinase 2 (MMP2) and Extracellular Signal-Regulated Kinase (ERK)

Aberrant protein activities are frequently observed in various diseases, especially cancer, where these proteins can promote oncogenesis and tumor progression. Many of those abnormal activities involve protein-protein interactions (PPI), which are often critical to protein activation and signal transduction. Developing chemical probes that can specifically interrogate and modulate PPI is attractive, as those probes promise therapeutic benefits and a better understanding of the underlying disease mechanisms. This dissertation presents our work of developing cyclic peptide-based probes that target two proteins: matrix metalloproteinase 2 (MMP2) and extracellular signal-regulated kinase (ERK), both of which are heavily implicated in cancer. In the first project, we report a cyclic peptide that can specifically inhibit MMP2 proenzyme activation, which decreased cancer cell invasion and migration abilities. In the second project, we demonstrate the potential of using the MMP2-targeting cyclic peptide as an imaging agent. In the final project, we showcase the development of cyclic peptide probes that bind to specific epitopes on the ERK protein and report its phosphorylation status