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Mass spectrometric identification of ligands selected from combinatorial libraries using gel filtration

✍ Scribed by Yuriy M. Dunayevskiy; Jan-Ji Lai; Cheryl Quinn; Frank Talley; Paul Vouros


Publisher
John Wiley and Sons
Year
1997
Tongue
English
Weight
226 KB
Volume
11
Category
Article
ISSN
0951-4198

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✦ Synopsis


There is a constant search for a successful analytical methodology to provide high throughput screening of combinatorial libraries against biological targets for identification of active ligands. Solid-phase screening assays offer faster isolation and identification of active analytes compared to the solution-based iterative methods. On the other hand, shift of combinatorial research to the creation of soluble non-peptide libraries, and limitations associated with the heterogeneous assays, creates a demand for a breakthrough technology for rapid and efficient screening of combinatorial libraries in solution. We demonstrated the efficient and rapid approach for selecting active ligands from a combinatorial mixture with subsequent identification of compounds by mass spectrometry. The procedure involves the use of a biological target molecule to physically isolate the active component in a mixture on a size exclusion medium. Then the ligands are identified using a combined liquid chromatography/capillary electrophoresis/mass spectrometry system. As a model system we used serum albumin and small molecules with different affinities to the protein.