Simultaneous imaging of protein-protein and protein-membrane interactions using molecular rotors

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Protein-protein interactions (PPIs) are integral to all biological processes, including those involved in disease pathways. Methods to study and quantify the effect of targeting these interactions in real time and at a single cell level are currently lacking. Molecular rotors, environmentally sensitive fluorophores, offer an exciting opportunity to quantitatively detect the function of a PPI inhibitor as a large change in fluorescence lifetime. We will develop novel peptide-rotor conjugates as tools to study the Bcl-2 family of PPIs, key oncology targets. Inhibition of these PPIs is inexorably linked to permeabilisation of the mitochondrial outer membrane. By employing rotors with complementary emission properties, we will study both PPI inhibition and membrane integrity simultaneously, offering unprecedented insight into these interlinked biological events.