Cathepsins are cysteine proteases involved in a number of stages of tumor development. In the September issue of Nature Chemical Biology, cathepsin activity is visualized in a cellular model of a tumor microenvironment. As a cellular safeguard, proteases are often generated in an inactive form and then processed to the active form only when the protein cutting activity is needed. Although there are many ways for detecting proteases, small molecules called "activity-based probes" that only react with active enzymes offer an important method for monitoring active proteases. Until now, using these probes for in vivo imaging has been difficult.
Matthew Bogyo and colleagues report a new method of fluorescence labeling of active proteases using activity-based probes. The authors chemically synthesized a molecule in which the fluorescence generated by one part of the molecule is "quenched"--or turned off--by another part of the molecule. When the probe reacts with an active protease, the quenching part of the molecule breaks off and a fluorescent signal can be seen. These probes were effective in imaging cathepsin in living cells.
The probes may prove useful for monitoring cathepsin activity in live mice, and the design of similar quenched probes targeting other proteases will provide important tools for investigating proteolytic function in vivo.
Matthew Bogyo (Stanford University, Stanford, CA, USA)
Abstract available online.
(C) Nature Chemical Biology.
Message posted by: Trevor M. D'Souza