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Direct mass spectrometric determination of bead bound compounds in a combinatorial lead discovery application
Author(s) -
Blom Karl F.,
Combs Andrew P.,
Rockwell Arlene L.,
Oldenburg Kevin R.,
Zhang JiHu,
Chen Tongming
Publication year - 1998
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/(sici)1097-0231(19980915)12:17<1192::aid-rcm302>3.0.co;2-0
Subject(s) - chemistry , bead , mass spectrometry , mass spectrum , chromatography , combinatorial chemistry , analytical chemistry (journal) , function (biology) , biological system , materials science , evolutionary biology , composite material , biology
A mass spectrometric strategy for the direct determination of the structures of compounds on active beads selected from combinatorial mixtures by ultrahigh throughput screening is presented. Complementary mass spectrometric data (exact mass and MS/MS spectra) were obtained in a single acquisition using automatic function switching. Analyses of these data produced unequivocal identifications of the structure in 70% of the cases. The automatic computer analyses generated definitve solutions in 80% of the analyses. The remainder of the beads contained mixtures of components or components not in the enumerated library (either by‐products or degradants of expected components). In these cases the identity of the compounds were conclusively deduced from manual interpretation of the mass spectral data. The putative identities of all active compounds were confirmed by resynthesis and comparison of the mass spectrometric data for the putative and authentic structures. © 1998 John Wiley & Sons, Ltd.