SYNTHESIS AND SCREENING OF SMALL-MOLECULE LIBRARIES ACTIVE IN BINDINGTO DNA

Five synthetic combinatorial libraries of 2,080 components each were s creened as mixtures for inhibition of DNA binding to two transcription factors. Rapid, solution-phase synthesis coupled to a gel-shift assay led to the identification of two compounds active at a 5- to 10-mu M concentration level, The likely mode of inhibition is intercalation be tween DNA base pairs, The efficient deconvolution through sublibrary s ynthesis augurs well for the use of large mixtures of small, nonpeptid e molecules in biological screens.