Affinity selection-mass spectrometry screening techniques for small molecule drug discovery |
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Authors: | Annis D Allen Nickbarg Elliot Yang Xianshu Ziebell Michael R Whitehurst Charles E |
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Affiliation: | Schering-Plough Research Institute, 320 Bent Street, Cambridge, MA 02139, United States. allen.annis@spcorp.com |
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Abstract: | Affinity selection-mass spectrometry (AS-MS) techniques assess the binding of candidate molecules to immobilized or soluble receptors, and these methods are gaining acceptance in high throughput screening laboratories as valuable complements to traditional drug discovery technologies. A diversity of receptor types have been evaluated by AS-MS, including those that are difficult to screen using traditional biochemical approaches. AS-MS techniques that couple liquid chromatography-MS with size-based separation methods, such as ultrafiltration, gel permeation, or size-exclusion chromatography, are particularly amenable to the demands of MS-based screening and have demonstrated the greatest success across a broad range of drug targets. MS measurements of receptor function have many of the same advantages as AS-MS screening and are increasingly used for drug discovery as well. |
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