MULTIDIMENSIONAL CHROMATOGRAPHY COUPLED WITH MASS-SPECTROMETRY FOR TARGET-BASED SCREENING

The synthesis of structural analogs and the process of drug discovery have evolved dramatically through recent advances in solid-phase synth esis reagents and automated screening systems. As molecular diversity strategies emerge, the need for automated target-based selection of le ad candidates becomes equally important. Multidimensional automated ch romatographic techniques coupled to electrospray ionization mass spect rometry facilitate the selection process and provide maximum character ization information in a single screening run. The capture of tightly bound affinity leads by target biomolecules, followed by subsequent re lease and high-resolution separation with sensitive detection, signifi cantly reduces the time required to identify and characterize lead com pounds. This automated multidimensional chromatographic approach coupl ed with mass spectrometry, Selectronics(TM), was used with several org anic and natural libraries to demonstrate an automated target-based sc reening technique to select for high-affinity binders as potential lea d compounds.