New Chemical Probe Technologies: Applications to Imaging, Target Identification and Drug Discovery

Hydrolases are enzymes that often play important roles in many common human diseases such as cancer, asthma, arthritis, atherosclerosis and infection by pathogens. Therefore tools that can be used to dynamically monitor their activity can be used as diagnostic agents, as imaging contrast agents and for the identification of novel classes of drugs. In the first part of this presentation, I will describe our efforts to design and synthesize small molecule probes that produce a fluorescent signal upon binding to tumor associated protease targets. We have identified probes that show tumor-specific retention, fast activation kinetics, and rapid systemic distribution making them useful for real-time fluorescence guided tumor resection and other diagnostic imaging applications. In the second half of the talk, I will present our recent advances using chemical probes to identify novel protease and hydrolase targets in pathogenic bacteria. This work has led to new imaging agents for Mycobacterium tuberculosis and the identification of novel virulence factors in Staphylococcus aureus that have the potential to be targeted with small molecules as a therapeutic strategy.