title: Evaluation of mass spectrometric methods applicable to the direct analysis of non-peptide bead-bound combinatorial libraries.
abstract: Electrospray, matrix-assisted laser desorption, and time-of-flight secondary ion mass spectrometry have been explored as possible methods for the identification of active members of molecular combinatorial libraries. All three methods are found to yield accurate molecular weight information about a target molecule angiotensin II antagonist synthesized on a 40-microns polystyrene bead. Structural identification is also possible by accurate mass measurements to eliminate candidate structures with the same nominal mass and by analysis of the fragmentation patterns. In addition, the secondary ion mass spectrometry measurements yield spatially resolved spectra from a single bead after exposure to a suitable gas which clips the covalent bond at the linking position. All three approaches appear to offer a viable screening strategy of non-peptide libraries without the use of additional molecular tags.
authors.affiliation: Department of Chemistry, Pennsylvania State University, University Park, 16802, USA.
authors.forename: C L
authors.initials: CL
authors.lastname: Brummel
authors.forename: J C
authors.initials: JC
authors.lastname: Vickerman
authors.forename: S A
authors.initials: SA
authors.lastname: Carr
authors.forename: M E
authors.initials: ME
authors.lastname: Hemling
authors.forename: G D
authors.initials: GD
authors.lastname: Roberts
authors.forename: W
authors.initials: W
authors.lastname: Johnson
authors.forename: J
authors.initials: J
authors.lastname: Weinstock
authors.forename: D
authors.initials: D
authors.lastname: Gaitanopoulos
authors.forename: S J
authors.initials: SJ
authors.lastname: Benkovic
authors.forename: N
authors.initials: N
authors.lastname: Winograd
mesh_terms: D000804:Angiotensin II / Q000037:antagonists & inhibitors; D005069:Evaluation Studies as Topic; D013058:Mass Spectrometry / Q000379:methods*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D000804:Angiotensin II