Selective Identification of Cooperatively Binding Fragments in a High‐Throughput Ligation Assay Enables Development of a Picomolar Caspase‐3 Inhibitor

Abstract

Putting the pieces together: A chemically reactive fluorescence polarization (FP) probe can be use to detect positively cooperative fragments through the overadditive binding of their ligation products. For confirmation, an stable derivative of the ligation product was prepared and found to be significantly more active than all previously reported caspase-3 inhibitors.