The proteasome, a large protein complex capable of proteolysis, is the primary means by which misfolded or unnecessary proteins are degraded in eukaryotes and archaea. Due to its size and complexity, the mechanisms underlying its function, including the way in which it processes substrates with different primary and secondary structure content, are poorly understood. Accordingly, experimental methods must be used that enable the spatio-temporal measurement of these functions. Biological nanopores are created when a transmembrane protein forms a nanometre-scale hole in a membrane. Building on their effective use in a broad range of applications, planned developments using nanopores include their integration into biosensors for the detection of analytes from blood. Recently, the group of Prof. Maglia developed a proteasome nanopore, paving the way to protein sequencing using nanopores. This significant development also provides an excellent platform for this proposed fundamental study into the function of the proteasome. In this work, PROTACs (proteolysis-targeting chimeras) will be used to target proteins with different primary and secondary structure content for polyubiquitination by the E3 ubiquitin ligase. Electrochemical measurements will be used to observe the impact of physico-chemical properties and structure on unfolding and degradation by the proteasome in real time. PROTACs enable selected proteins to be targeted for degradation from mixtures or biological samples. This project is expected to have a significant impact on our understanding of the function of the proteasome, as well as in the areas of peptide sequencing and biosensors for tailored medicine.