Single bead characterization using analytical constructs: Application to quality control of libraries

Analytical construct technology has been successfully applied to the single -bead analysis of a split-mix combinatorial library. Substrates can be rele ased from the resin by conventional cleavage for biological screening. Alte rnatively, for the purpose of analysis and quality control, cleavage at an orthogonal construct linker produces an analytical fragment incorporating t he substrate. This analytical fragment is highly sensitized to electrospray mass spectrometry (ESI-MS) and is easily identified by isotope labeling. T he construct cleavage rendered readily visible even those compounds that cl early could not be seen by conventional cleavage and mass spectrometry anal ysis. A H-1 NMR control experiment proved that the compounds cleaved conven tionally were, however, present in the sample in good yield and purity, In view of the data obtained, we think that this is a significant and importan t step toward solving our current quality control problems,