Microautoradiographic identification of receptor-ligand interactions in bead-supported combinatorial libraries

We have developed a method for the microautoradiographic screening of bead-supported combinatorial libraries with radiolabeled receptor molecules which allows for the identification of individual radioactive beads under a low-power light microscope. A 14C-labeled macrobicyclic receptor was assayed against an encoded combinatorial tripeptide library to establish the efficacy of the technique. The described microradiographic scheme promises to be advantageous in cases where the receptors show only modest discrimination between the members of the screened library or in cases where the individual beads provide only very low radioactivity levels after the equilibration with the radiolabeled receptor.