Phosphorylation Sensors

The ‘bioprobes’ group within the team is developing new probes and technique -- all of which involve some element of synthetic or semi-synthetic chemistry -- which can be applied to a number of problems in chemical biology, including the analysis of protein complexes.

Catalyzed by kinases, Ser/Thr and Tyr phosphorylation is a vital mechanism of intracellular regulation. With more than 500 different kinases encoded in the human genome, however, closely related enzymes will inevitably phosphorylate some of the same substrates. Thus, simple, sensitive and selective tools for monitoring target kinase activities are invaluable in academic and pharmaceutical settings. In order to address issues of assaying ease we are developing reporters of kinase activity that exploit the chelation-enhanced fluorescence of the sulfonamido-oxine (Sox) family of chromophores. This fluorescence-based method allows us to design highly selective chemosensors either by synthesizing peptide- or protein-based probes for virtually any kinase of interest. This work can be applied for new drug discovery in a high-throughput manner, and also for unraveling the multifarious signaling cascades in which these enzymes are pivotal. Current efforts focus on the design and synthesis of next generation probes, based upon the chelation-enhanced fluorescence strategy, that show ideal photophysical properties for cellular imaging and highly miniaturized devices.