Affinity Selection ‐Mass Spectrometry for the Discovery of Pharmacologically Active Compounds from Combinatorial Libraries and Natural Products

AbstractInvented to address the high ‐throughput screening (HTS) demands of combinatorial chemistry, affinity selection‐mass spectrometry (AS‐MS) utilizes binding interactions between ligands and receptors to isolate pharmacologically active compounds from mixtures of small molecules and then relies on the selectivity, sensitivit y and speed of mass spectrometry to identify them. No radiolabels, fluorophores or chromophores are required. Although many variations of AS‐MS have been devised, three approaches have emerged as the most flexible, productive and popular, and they differ primarily in how ligand‐receptor complexe s are separated from non‐binding compounds in the mixture. These are pulsed ultrafiltration (PUF) AS‐MS, size exclusion chromatography (SEC) AS‐MS, and magnetic microbead affinity selection screening (MagMASS). PUF and SEC AS‐MS are solution‐phase screening approaches, and MagMASS uses rec eptors immobilized on magnetic microbeads. Because pools of compounds are screened using AS‐MS, each containing hundreds to thousands of potential ligands, hundreds of thousands of compounds can be screened per day. AS‐MS is also compatible with complex mixtures of chemically diverse natural pro ducts in extracts of botanicals, fungi and microbial cultures, which often contain fluorophores and chromophores that can interfere with convention HTS. Unlike conventional HTS, AS‐MS may be used to discover ligands binding to allosteric as well as orthoste...
Source: Journal of Mass Spectrometry - Category: Chemistry Authors: Tags: SPECIAL FEATURE: TUTORIAL Source Type: research