title: Rapid characterization of combinatorial libraries using electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry.
abstract: The relatively new field of combinatorial chemistry has enabled researchers to create large mixtures of compounds that can be screened for leads in developing potential drug candidates. The new synthetic method has also created a need for better procedures to analyze the complex mixtures that are generated. The immediate goal in most cases is to verify the synthetic procedure and to determine the purity and completeness of the library sample before binding studies are initiated. We report here a method to rapidly characterize small-molecule combinatorial libraries in solution. All combinatorial library samples were synthesized by combining a core molecule bearing two acid chloride functionalities with various amino acids to generate libraries of 36, 78 and 120 components. Using electrospray ionization fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICR-MS) we were able to identify 70-80% of the library components. All samples were analyzed as mixtures by direct infusion without chromatographic separation. Furthermore, nominally isobaric components could be resolved and identified through exact mass assignments without tandem mass spectrometery. ESI-FTICR-MS is a rapid and convenient tool for the characterization of small-molecule libraries. The method is especially useful for the analysis of larger libraries that contain many nominally isobaric components and impurities.
authors.affiliation: Department of Chemistry, Barnett Institute, Northeastern University, Boston, MA 02115, USA.
authors.forename: A S
authors.initials: AS
authors.lastname: Fang
authors.forename: P
authors.initials: P
authors.lastname: Vouros
authors.forename: C C
authors.initials: CC
authors.lastname: Stacey
authors.forename: G H
authors.initials: GH
authors.lastname: Kruppa
authors.forename: F H
authors.initials: FH
authors.lastname: Laukien
authors.forename: E A
authors.initials: EA
authors.lastname: Wintner
authors.forename: T
authors.initials: T
authors.lastname: Carell
authors.forename: J
authors.initials: J
authors.lastname: Rebek
mesh_terms: D002626:Chemistry, Pharmaceutical; D017357:Cyclotrons; D015195:Drug Design; D013058:Mass Spectrometry; D008956:Models, Chemical; D019151:Peptide Library; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D019151:Peptide Library