. Noninvasive optical imaging of cysteine protease activity using fluorescently quenched activity-based probes. Nature Chemical Biology. 2007 Sep 9;


We have generated a series of quenched near-infrared fluorescent activity-based probes (qNIRF-ABPs) that covalently target the papain-family cysteine proteases shown previously to be important in multiple stages of tumorigenesis. These 'smart' probes emit a fluorescent signal only after covalently modifying a specific protease target. After intravenous injection of NIRF-ABPs into mice bearing grafted tumors, noninvasive, whole-body imaging allowed direct monitoring of cathepsin activity. Importantly, the permanent nature of the probes also allowed secondary, ex vivo biochemical profiling to identify specific proteases and to correlate their activity with whole-body images. Finally, we demonstrate that these probes can be used to monitor small-molecule inhibition of protease targets both biochemically and by direct imaging methods. Thus, NIRF-ABPs are (i) potentially valuable new imaging agents for disease diagnosis and (ii) powerful tools for preclinical and clinical testing of small-molecule therapeutic agents in vivo.


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  1. Bogyo and colleagues developed a new generation of fluorescent quenched activity-based probes that can be used to visualize the dynamics of active proteases in whole animals. These elegant probes combine the “quenching” feature, which offers the advantage of igniting only the active protease, with the near-infrared fluorescent conjugates to reduce background in in-vivo imaging.

    Accumulating evidence supports the involvement of cysteine proteases in AD pathogenesis. For example, our recent study provides evidence that cathepsin B plays a role in amyloid-β degradation and clearance, suggesting that the deficiency and dysregulation of cysteine proteases may lead to Aβ accumulation. To fully understand the improper functions of cysteine proteases in AD, we need to be able to detect the activity of specific cysteine protease at the point of action and in real time. With a proper delivery method, the probes developed by Bogyo and colleagues may be well suited to do just that.

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