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A Novel and Rapid Encoding Method Based on Mass Spectrometry for “One-Bead-One-Compound” Small Molecule Combinatorial Libraries
journal contribution
posted on 2003-04-29, 00:00 authored by Aimin Song, Jinhua Zhang, Carlito B. Lebrilla, Kit S. LamA novel and efficient encoding method based on mass spectrometry for “one-bead-one-compound”
small molecule combinatorial libraries has been developed. The topologically segregated bifunctional resin
beads with orthogonal protecting groups in the outer and inner regions are first prepared according to our
previously published procedure. Prior to library synthesis, the inner core of each bead is derivatized with
3−4 different coding blocks on a cleavable linker. Each functional group on the scaffold is encoded by an
individual coding block containing a functional group with the same chemical reactivity. During the library
synthesis, the same chemical reactions take place on the scaffold (outer layer of the bead) and coding
blocks (inner core of the bead) concurrently. After screening, the coding tags in the positive beads are
released, followed by molecular mass determination using matrix-assisted laser desorption ionization Fourier
transform mass spectrometry. The chemical structure of library compounds can be readily identified
according to the molecular masses of the coding tags. The feasibility and efficiency of this approach were
demonstrated by the synthesis and screening of a model small molecule library containing 84 672 member
compounds, with a model receptor, streptavidin. Streptavidin binding ligands with structural similarity (17)
were identified. The decoding results were clear and unambiguous.