Direct screening of solution phase combinatorial libraries encoded with externally sensitized photolabile tags

Solution phase combinatorial chemistry holds an enormous promise for modern drug discovery. Much needed are direct methods to assay such libraries for binding of biological targets. An approach to encoding and screening of solution phase libraries has been developed based on the conditional photorelease of externally sensitized photolabile tags. The encoding tags are released into solution only when a sought-for binding event occurs between the ligand and the receptor, outfitted with an electron-transfer sensitizer. The released tags are analyzed in solution revealing the identity of the lead ligand or narrowing the range of potential leads.