The development of techniques to screen one-bead-one-compound (OBOC) libraries remains a critical step in identifying small molecules that bind target proteins. While great strides have been made, there remains a… Click to show full abstract
The development of techniques to screen one-bead-one-compound (OBOC) libraries remains a critical step in identifying small molecules that bind target proteins. While great strides have been made, there remains a need to continue to develop OBOC screening techniques that not only reliably identify hit molecules but also can distinguish poor from excellent binders in a single screen. Similarly, relatively strong binding between a small molecule and protein target is required to be considered a hit from the initial pool of screened molecules. Here, we present the framework for a method to screen OBOC libraries using proteins and antibodies stained with a near-infrared (NIR)-emitting fluorophore. These labeled proteins provide significant signal at very low concentrations because of their fluorescence quantum yield. This work revealed that we can detect proteins and antibodies interacting with a known binding partner at low nanomolar concentrations; binding is specific, and known binders to carbonic anhydrase can be detected and ranked.
               
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