title: Multidimensional chromatography coupled with mass spectrometry for target-based screening.
abstract: The synthesis of structural analogs and the process of drug discovery have evolved dramatically through recent advances in solid-phase synthesis reagents and automated screening systems. As molecular diversity strategies emerge, the need for automated target-based selection of lead candidates becomes equally important. Multidimensional automated chromatographic techniques coupled to electrospray ionization mass spectrometry facilitate the selection process and provide maximum characterization information in a single screening run. The capture of tightly bound affinity leads by target biomolecules, followed by subsequent release and high-resolution separation with sensitive detection, significantly reduces the time required to identify and characterize lead compounds. This automated multidimensional chromatographic approach coupled with mass spectrometry, Selectronics, was used with several organic and natural libraries to demonstrate an automated target-based screening technique to select for high-affinity binders as potential lead compounds.
authors.affiliation: PerSeptive Biosystems Inc., Framingham, MA 01701, USA.
authors.forename: Y F
authors.initials: YF
authors.lastname: Hsieh
authors.forename: N
authors.initials: N
authors.lastname: Gordon
authors.forename: F
authors.initials: F
authors.lastname: Regnier
authors.forename: N
authors.initials: N
authors.lastname: Afeyan
authors.forename: S A
authors.initials: SA
authors.lastname: Martin
authors.forename: G J
authors.initials: GJ
authors.lastname: Vella
mesh_terms: D000591:Amino Acid Isomerases / Q000187:drug effects / Q000378:metabolism; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism; D002845:Chromatography / Q000295:instrumentation / Q000379:methods*; D002846:Chromatography, Affinity / Q000295:instrumentation / Q000379:methods; D003574:Cytochrome c Group / Q000187:drug effects / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D004353:Drug Evaluation, Preclinical / Q000295:instrumentation / Q000379:methods*; D006360:Heat-Shock Proteins / Q000187:drug effects / Q000378:metabolism; D013058:Mass Spectrometry / Q000379:methods*; D019696:Peptidylprolyl Isomerase; D022021:Tacrolimus Binding Proteins; D013762:Tetrahydrofolate Dehydrogenase / Q000187:drug effects / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D003574:Cytochrome c Group; D004268:DNA-Binding Proteins; D006360:Heat-Shock Proteins; D013762:Tetrahydrofolate Dehydrogenase; D000591:Amino Acid Isomerases; D022021:Tacrolimus Binding Proteins; D019696:Peptidylprolyl Isomerase