DIRECT MASS-SPECTROMETRIC DETERMINATION OF BEAD BOUND COMPOUNDS IN A COMBINATORIAL LEAD DISCOVERY APPLICATION

A mass spectrometric strategy for the direct determination of the stru ctures of compounds on active beads selected from combinatorial mixtur es by ultrahigh throughput screening is presented. Complementary mass spectrometric data (exact mass and MS/MS spectra) were obtained in a s ingle acquisition using automatic function switching. Analyses of thes e data produced unequivocal identifications of the structure in 70% of the cases. The automatic computer analyses generated definitive solut ions in 80% of the analyses. The remainder of the beads contained mixt ures 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 inter pretation of the mass spectral data. The putative identities of all ac tive compounds were confirmed by resynthesis and comparison of the mas s spectrometric data for the putative and authentic structures. (C) 19 95 John Wiley & Sons, Ltd.