Probing the character of proteins
A team from The Scripps Research Institute has developed a high throughput technology that can screen compound libraries against proteins whose biochemical activities are poorly characterized.1 The method, which relies on fluorescent activity-based chemical probes to identify hits, can screen libraries containing tens of thousands of compounds, an increase of two orders of magnitude over the capacity of existing activity-based protein binding screens.
About 30-50% of human proteins have unknown biochemical activity2 and thus are not amenable to conventional high throughput screens, which require detailed knowledge of a target protein's activity or binding partners. Activity-based protein profiling (ABPP) overcame these limitations by using chemical probes capable of binding the active site on a large number of mechanistically related enzymes, thus obviating the need for specific information about a given target. But the approach required gel-based assays-a laborious and time-consuming process that limited activity-based screens to small libraries...