Structure-guided Peptide Engineering for Aurora B Kinase Protein-Protein Interaction

Ziel

Current inhibitors of the cancer target Aurora B kinase are limited by toxicity due to poor selectivity. The SPEAK-PPI project will overcome this by developing first-in-class peptide probes that selectively target the unique protein-protein interaction (PPI) with its co-activator INCENP—an unexploited therapeutic opportunity. Using a rational, structure-guided methodology, this project will design and synthesise 'stapled peptides' to disrupt this interaction. This approach locks peptides into their bioactive conformation to enhance binding affinity, stability, and cell permeability, thus bridging cutting-edge computational design with translational drug discovery.

This fellowship is founded on a powerful synergy between the host and fellow. It merges the host's (Prof. Wilson) world-leading expertise in peptidomimetics chemistry and biophysical analysis with the fellow's (Dr. Choi) experience in structure-based drug design (SBDD) and preclinical development of mitotic kinase inhibitors. This two-way knowledge transfer creates an ideal team to deliver a validated chemical probe that will unlock Aurora B biology and establish a novel, less toxic therapeutic concept for hard-to-treat cancers. Crucially, the fellowship will provide the researcher with essential multidisciplinary training in peptide chemistry, biophysics, and drug discovery, fostering their transition to an independent research leader in academia or industry within the EU.