A future development for drug discovery using the GPC spin column/ESI-MS technique is to eliminate the HPLC/UPLC instrumentation in the analysis of the GPC spin column eluates and achieve the needed separation on a millisecond scale by use of an ion mobility (IM) interface to the ESI-Tof mass spectrometer. The ion mobility interface resolves compounds on the basis of their resistance to flow under an applied electric field and a buffer gas due to the differences in collision cross-sections (shapes, charges, masses) of the molecules. The IM/MS technique has the unique capability of resolving ligands that are structural isomers. This approach has been demonstrated for drug screening by Clemmer and co-workers for identifying members of a combinatorial peptide library that bind to ribonuclease S-protein using affinity selection chromatography for non-covalent binders and ESI/IM/MS for characterization of the ligands .
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